- TOMLINSON B;MAK V W L;CHU T T W;TSUI T;LEE V W Y;
Objective To examine the relationship of single-nucleotide polymorphisms(SNPs)in candidate genes with the lipid responses to simvastatin.Methods Chinese patients were treated with simvastatin 40 mg daily for at least 6 weeks.20 SNPs in 11 genes were genotyped.Results 95 patients age(mean±SD)57.5±10.6 years completed the treatment.The Adiponectin 45T>G polymorphism was significantly related to absolute reductions in total cholesterol(TC)and LDL-cholesterol with a trend(P=0.053)for percentage reductions in TC(TT∶TG∶GG=-38.4%∶-35.6%∶-32.6%).Similar findings were seen with LDL-Receptor(LDLR)SNPs(2052T>C and 1866C>T)with absolute reductions in TC and LDL-cholesterol significantly associated.The Breast Cancer Resistance Protein(ABCG2)421C>A polymorphism was related(P<0.05)to HDL-cholesterol response(CC∶CA∶AA=+0.50%∶-5.73%∶-11.41%).Conclusions Adiponectin,LDLR and ABCG2 SNPs had some influence on the lipid responses to simvastatin.
2008年S1期 v.25 1页 [查看摘要][在线阅读][下载 6K] [下载次数：18 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：71 ] - WONG Wing-tak;LEUNG Fung-ping;WONG Ricky Ngok Shun;
Objective To investigate possible mechanisms underlying the antioxidant property(1)and the in vitro vasodilator effects(2)of the two ginsenosides,Rb1 and Rg1,in isolated rat renal and cerebral arteries.Methods Arterial rings were mounted in a multi-channel myograph for recording of isometric tension.To examine the antioxidant activity,some rings were exposed to a free radical-generating reaction(hypoxanthine and xanthine oxidase)with and without pre-treatment with ginsenosides.The calcium antagonistic effects were tested on rings contracted by membrane depolarization in elevated extracellular potassium ions,a condition that promoted Ca2+ influx in vascular smooth muscle cells.Results Ginsenosides protected endothelial function(endothelial nitric oxide-dependent relaxation)against oxidative stress;(2)ginsenoside Rb1 reduced the high K+-induced contractions of both renal and cerebral arteries while ginsenoside Rg1 relaxed the rat cerebral artery but not the renal artery.Conclusions Ginsenosides are vaso-protective via(1)the antioxidant activity which protects endothelial cell function and(2)the inhibition of Ca2+ influx through voltage-sensitive Ca2+ channels in vascular smooth muscle.The vasodilator effects may suggest the potential preventive or therapeutic values of ginsenosides against stroke and renal hypertension.
2008年S1期 v.25 2页 [查看摘要][在线阅读][下载 7K] [下载次数：27 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：60 ] - CHO Chi-hin;
Objective Mucus forms the physical barrier along the gastrointestinal(GI)tract.It plays an important role to prevent mucosal damage and inflammation.Our previous finding showed that antibacterial peptide 'cathelicidin' increased mucus thickness and prevented inflammation in the colon.In the current study,we examined the protective mechanisms by which the peptide increased mucus synthesis in vitro.Methods Human colonic cell line(HT-29)was used to assess the stimulatory action of cathelicidin on mucus synthesis which was measured by the D-[6-3H] glucosamine incorporation assay.Results Human cathelicidin(LL-37)dose-dependently(10-40 μg·mL-1)and significantly stimulated mucus synthesis.Real-time PCR data showed that addition of LL-37 induced more than 50% increase in MUC1 and MUC2 mRNA levels.Treatment with MUC1 and MUC2 siRNAs normalized the stimulatory action of LL-37 on mucus synthesis.LL-37 also activated the phosphorylation of mitogen-activated protein(MAP)kinase in the cells.A specific inhibitor of the MAP kinase pathway,U0126,completely blocked the increase of MUC1 and MUC2 expression as well as mucus synthesis by LL-37.Conclusions Taken together LL-37 stimulates mucus synthesis through the activation of MUC1 and MUC2 expression and the MAP kinase pathway in human colonic cells.
2008年S1期 v.25 3页 [查看摘要][在线阅读][下载 6K] [下载次数：38 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：49 ] - NG K Y;WONG Y H;WISE H;
Objective The glial cells of the central nervous system are involved in tripartite signaling,therefore we have been investigating the relationship between sensory neurons and non-neuronal cells in isolated preparations of dorsal root ganglia(DRG).Methods The mixed cell cultures of dissociated DRG cells were separated to yield enriched fractions of IB4-positive cells(small diameter,non-peptidergic cells),IB4-negative cells(small diameter,peptidergic cells,and large diameter cells),and non-neuronal cells(principally satellite glial cells,Schwann cells and fibroblasts).Adenylyl cyclase activity was assayed by measuring production of [3H]cAMP from cells preloaded with [3H]adenine.Results PGE2 and the PGI2 mimetic cicaprost stimulated adenylyl cyclase activity which was inhibited by ONO-AE3-208(EP4 antagonist)or CAY10441(IP antagonist)with estimated pA2 values of 8.9 and 8.2,respectively.Surprisingly,both PGE2 and cicaprost-stimulated [3H] cAMP production was greatest in the non-neuronal cell preparation.Furthermore,when the number of non-neuronal cells was kept constant and the number of neuronal cells was increased,we observed a progressive decrease in prostanoid-stimulated activity.Conclusions Sensory neurons appear to regulate prostanoid receptor-mediated cell signaling in non-neuronal cells within the DRG.
2008年S1期 v.25 4页 [查看摘要][在线阅读][下载 7K] [下载次数：20 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：66 ] -
Green tea has received much attention as protective agent against cardiovascular disease and cancer,the two primary targets of preventive medicine.Since our first demonstration in 1999 of the involvement of endothelium-derived nitric oxide in the acute vasodilator effect of green tea polyphenols,several new vascular protective effects of green tea catechins have been identified.Theaflavins are another class of polyphenol pigments found in black tea,however,little is known about their bioactivity in the vascular system.We have recently demonstrated that black tea and its theaflavins cause relaxations of rat aortas via endothelial nitric oxide-dependent mechanisms and the tea polyphenols are very effective in protecting endothelial function agonist oxidative stress.The present results support the vascular benefit of consumption of black tea,which is equal to that of drinking green tea in terms of their endothelial cell protection and antioxidant capacity.
2008年S1期 v.25 5页 [查看摘要][在线阅读][下载 4K] [下载次数：37 ] |[网刊下载次数：0 ] |[引用频次：1 ] |[阅读次数：93 ] - JOSHUA K S Ko;Kathy K W Auyeung;
Objective Many Asian countries including China,Japan and Korea have very high incidence of gastric cancer,in which about 42% cases occur in mainland China.The precise targets and underlying mechanisms are not well understood.Our previous study revealed that Astragalus saponins(AST)showed promising effects on the suppression of the growth of HT-29 human colon cancer cells and tumor xenograft by inhibiting cell proliferation and promoting apoptosis.In the present study,we investigated the anti-carcinogenic effects of AST in AGS human gastric adenocarcinoma cells and attempted to elucidate the underlying mechanisms.Methods Growth inhibition of AGS cells was determined by using the MTT viability test.Involvement of different members of the apoptotic cascade and other growth-related factors was explored by assessment of their protein expression using Western blot analysis.Distribution of cells in different phases of the cell cycle was assessed by flow cytometry.Results Our data indicate that AST induced growth-inhibition and apoptosis in AGS cells by activating caspase 3 with subsequent poly(ADP-ribose)polymerase(PARP)cleavage.Cell cycle arrest at the G2/M phase had been observed in AST-treated AGS cells.The anti-proliferative effect of AST was associated with modulation of cyclin B1 and p21.We then demonstrate that AST could downregulate the expression of VEGF,of which interaction with its receptors is important for angiogenesis during tumor formation.Conclusions Our findings suggest that AST is an effective agent in gastric cancer treatment by inducing cell cycle arrest and apoptosis,of which anti-angiogenesis could be an alternative mode of action.
2008年S1期 v.25 6页 [查看摘要][在线阅读][下载 7K] [下载次数：43 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：58 ] - PAUL M Vanhoutte;
Endothelial cells can initiate contraction(constriction)of the vascular smooth muscle cells that surround them.Such endothelium-dependent,acute increases in contractile tone can be due to the withdrawal of the production of nitric oxide,to the production of vasoconstrictor peptides(angiotensin II,endothelin-1),to the formation of oxygen-derived free radicals(superoxide anions)and/or the release of vasoconstrictor metabolites of arachidonic acid.The latter have been termed endothelium-derived contracting factor(EDCF)as they can contribute to moment-to-moment changes in contractile activity of the underlying vascular smooth muscle cells.To judge from animal experiments,EDCF-mediated responses are exacerbated when the production of nitric oxide is impaired as well as by aging,spontaneous hypertension and diabetes.To judge from human studies,they contribute to the blunting of endothelium-dependent vasodilatations in aged subjects and essential hypertensive patients.Since EDCF causes vasoconstriction by activation of the TP-receptors on the vascular smooth muscle cells,selective antagonists at these receptors prevent endothelium-dependent contractions,and curtail the endothelial dysfunction in hypertension and diabetes.
2008年S1期 v.25 7页 [查看摘要][在线阅读][下载 5K] [下载次数：20 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：50 ] Objective To investigate the protective effects of Salvianolic acid B(Sal B)on hydrogen peroxide(H2O2)-induced injury in human umbilical vein endothelial cells(HUVECs).Sal B is considered as one of the most active anti-oxidant and the major pharmacological component of the herb,Salvia miltiorrhiza.Its beneficial effects include hepatoprotection,elicitation of endothelium-dependent vasodilation,lowering blood pressure in hypertension,inhibition of HIV-1 replication and suppressing inflammatory cytokine-stimulated endothelial adhesiveness to human monocytic cells by its strong antioxidant activities.Methods Treatment with H2O2 significantly decreased the cell viability and increased the lactate dehydrogenase(LDH)leakage that is an apoptotic feature.Pretreatment with Sal B prevented significantly from H2O2-induced cell apoptosis and other damages in a concentration-dependent manner.The mechanism of Sal B protection was studied with two-dimensional gel electrophoresis(2-DE)coupled to hybrid quadrupole time-of-flight mass spectrometry(Q-TOF)mass spectrometer.Results Data base searching implicated glucose-regulated protein 78(GRP78),a central regulator for ER stress,was up-regulated in Sal B-exposed HUVECs.After exposure to Sal B,the level of activating transcription factor 4(ATF4)was raised,with a transient phosphorylation of the α subunit of eukaryotic translation initiation factor(eIF2α).Knock-down of GRP78 by siRNA significantly reduced protective effects of Sal B.Conclusions These results suggest that Sal B-induced GRP78 up-regulation via phosphorylation of eIF2α and resultant translation of ATF4.And up-regulation of ER chaperones induced by Sal B may play an important role in protecting human endothelial cells from oxidative stress-induced cellular damage.
2008年S1期 v.25 8页 [查看摘要][在线阅读][下载 8K] [下载次数：35 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：53 ] -
Objective Purification and Standardization of Chinese herbal extracts became a hot topic since last decade.Though traditional Chinese medicine(TCM)has been used as a mixture from several herbs for centuries,it has been drawn much attention for studying the standardized Chinese herbs using modern technology.Methods Recently,we compared purified Salvia miltiorrhiza extract(PSME)with angiotensin-converting enzyme inhibitor,Ramipril,in in vitro experiments and also in vivo using animal model of myocardial infarction.Results PSME was found to have a significantly higher trolox equivalent antioxidant capacity which indicated a great capacity for scavenging free radicals.PSME could also prevent pyrogallo red bleaching and DNA damage.After 2 weeks treatment with PSME or Ramipril,survival rates of rats with experimental myocardial infarction were marginally increased(68.2% and 71.4%)compared with saline(61.5%).In another recent study,we evaluated the cardioprotective effects of PSME on myocardial ischemia/reperfusion injury in isolated rat hearts and in hypoxic vascular smooth muscle cells.We found that PSME treated hearts showed significant postischemic contractile function recovery(develop pressure recovered to 44.2±4.9% versus 17.1±5.7%,P<0.05;maximum contraction recovered to 57.2±5.9% versus 15.1±6.3%,P<0.001;maximum relaxation restored to 69.3±7.3% versus 15.4±6.3%,P<0.001 in PSME and control group respectively).Conclusions Significant elevated in end-diastolic pressure,which indicated LV stiffening in PSME hearts might be resulted by exceed dose of PSME used.Purified and standardized Chinese herb could provide an alternative regimen for the prevention of ischemic heart disease.
2008年S1期 v.25 9页 [查看摘要][在线阅读][下载 7K] [下载次数：25 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：47 ] Objective To investigation on novel pharmacological target against pulmonary hypertension.It was recognized in the recent years that pulmonary hypertension(PHT)compromised of four components,i.e.vasoconstriction,hyperplasia,micro thrombosis and inflammation of pulmonary vasculature.Pulmonary vascular hyperplasia is a hallmark pathologic feature of pulmonary hypertension.Hyperplasia of rat pulmonary artery smooth muscle cells(PASMCs)was significantly increased,and PASMCs from rats or human beings with PHT grow faster than those from control subjects when stimulated by serotonin or serum.Pulmonary hypertension(PHT)is the major cause of right ventricular hypertrophy and eventually right heart failure.5-hydroxytraptamine(5-HT)as mitogen for vascular smooth muscle cells plays an important role in the development of PHT.It is known that selective serotonin re-uptake inhibitors(SSRIs)restrain 5-HT internalization.Therefore,this study was aimed to investigate if SSRIs may have protective effect against monocrotaline(MCT)-induced right ventricular hypertrophy.Methods induced chronic pulmonary hypertension in Wistar rats was established;fluoxetine and sertraline(2,10 mg·kg-1·d-1 were administered by gavages.3 w after MCT injection,right ventricular index(RVI),pulmonary artery pressure(PAP),heart and lung morphology were measured or investigated.5-HT transporter(SERT)assayed by RT-PCR or Western blot.Results MCT-Results RVI was significantly increased in MCT group(P<0.01 vs control)and reduced to by fluoxetine(10 mg·kg-1·d-1)and 0.42±0.04 by Sertraline(10 mg·kg-1·d-1)(both P<0.05 vs MCT).PAP increased significantly by MCT(P<0.01 vs control).Fluoxetine(10 mg·kg-1·d-1),or sertraline(10 mg·kg-1·d-1)attenuated MCT-induced increase of PAP,respectively(both P<0.05 vs MCT).MCT raised significantly Pulmonary artery muscularization(P<0.01 vs control),and attenuated by fluoxetine or sertraline(P<0.01 vs MCT).MCT increased SERT mRNA and protein expression,and both were significantly attenuated by fluoxetine or sertraline,respectively.Conclusions SSRIs protect against MCT-induced right ventricular hypertrophy,RVI,PAP,Pulmonary artery muscularization,which may be relevant to inhibition of SERT and the results suggest that SERT may be a novel pharmacological target against pulmonary hypertension.
2008年S1期 v.25 10页 [查看摘要][在线阅读][下载 10K] [下载次数：22 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：69 ] -
Objective To elucidate the BRCA1 participated mechanism of genesis and development of sporadic breast cancer through detect the statues of BRCA1 and analysis the relationship with the pathologic and clinic parameters.Methods BRCA1 statues were respectively analyzed in frozen samples or paraffine fixed sporadic breast carcinoma and benign breast tissues by three methods:protein expression by immunohistochemistry(IHC),the methylation of BRCA1 promoter by methylation specific PCR(MSP),gene copy number by interphase fluorescence in situ hybridization(FISH).Results 14.2%(29/204)cases were detected hypermethylation of BRCA1 promoter in sporadic breast cancer.BRCA1 mean copy number in sporadic breast cancer(1.70±0.14)less than those in benign tissues(2.03±0.08,P<0.05),and in sporadic breast cancer with hypermethylation of BRCA1(1.62±0.09)significantly less than in those without hypermethylation(1.84±0.26,P<0.05).The loss copy related to the methylation of BRCA1 promoter.There were significant of 41.1%(88/214)cases no BRCA1 nuclei expression in sporadic breast cancers.Loss expression of BRCA1 had significant correlation with higher histological stages,axillary's lymph nodal metastasis(P<0.01),lower expression of ERα,and overexpression of HER-2 protein(P<0.01).Conclusions There are BRCA1 methylations,loss BRCA1 gene copy and loss protein expression in the sporadic breast cancer,the three statues of BRCA1 is correlated to each other;and the loss expression of BRCA1 protein related to part of pathology and clinic parameters.
2008年S1期 v.25 11页 [查看摘要][在线阅读][下载 7K] [下载次数：32 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：52 ] Objective To determine the inhibitory effects of 21 resveratrol derivatives and 3 natural curcuminoids on lipopolysaccharide(LPS)-induced Nitric oxide(NO)and tumor necrosis factor-alpha(TNF-α)production in microglia and their structure-activity relationships.Methods Cell viability was evaluated by the MTT reduction assay.Accumulation of nitrite(NO2-)in culture supernatant fluids was measured by the Griess reaction.Sodium nitroprusside(SNP)(2.5 mM)solution was used to determine the scavenging activities of these compounds.The levels of TNF-α in the culture medium were measured by using an ELISA kit.Semi-quantitative RT-PCR analysis was used to determine the mRNA levels of inducible NOS(iNOS)and TNF-α.Results It was found,for the first time,that certain resveratrol derivatives that have 3,5-dimethoxyl groups in the A-ring,such as(E)-4-(3,5-dimethoxystyryl)phenol(pterostilbene,compound 2),or have substituted the B-ring of resveratrol with quinolyl,such as(E)-5-[2-(quinolin-4-yl)vinyl]benzene-1,3-diol(compound 18)and(E)-4-(3,5-dimethoxystyryl)quinoline(compound 19),strongly inhibited NO production.Compounds 2,18,and 19 reduced LPS-induced protein and mRNA expression of inducible NO synthase(iNOS),but did not display direct NO-scavenging activity up to 30 μM in sodium nitroprusside(SNP)solution.Moreover,compounds 2,18,and 19 could also significantly inhibit the production of TNF-α by LPS-activated microglia.Furthermore,we found the demethoxy derivatives of curcumin have more potent inhibition activity on NO and TNF-α releasing in activated-microglia.Conclusions In the present study we compared the activated-microglia inhibition effect of resvertrol,curcumin and their derivatives and provided a glance of the structure-activity relationships of these compounds,the information is beneficial to design new potent compounds which can provide better therapeutic implications for various neurodegenerative diseases.
2008年S1期 v.25 12页 [查看摘要][在线阅读][下载 9K] [下载次数：64 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：79 ] - UENO Yuko;SAKURAI Hiroaki;SAIKI Ikuo;
Objective To investigate the antitumor effects of VnA,the total alkaloids isolated from Veratrum Nigrum L.var.ussuriense Nakai("Wusuli Lilu" in Chinese),and the underlying mechanisms with emphasis on its anti-metastatic effects.Methods The effects of VnA on in vitro proliferation,invasion,migration and adhesion in Colon26-L5 cells were investigated.The effect of VnA on experimental lung metastasis of Colon26-L5 cells in mice was also be studied by means of measuring the numbers of tumor colonies in lungs after single i.v.administration of Colon26-L5 cells to mice followed by q.d.i.p VnA for consecutive 14 days.The effect of VnA on the production of matrix metalloproteinases(MMPs)from Colon26-L5 cell in vitro was determined by means of gelatin zymography.Results In in vitro experiments,VnA was found to significantly reduce the number of tumor colonies at dosage of 20.0-40.0 μg·kg-1.In in vitro experiments,VnA inhibited the adhesion(at 1.6-12.5 μg·mL-1)and migration(at 3.1-50.0 μg·mL-1)of Colon26-L5 cell to extracellular matrix components and suppressed invasion into reconstituted basement membrane matrigel(at 3.1-50.0 μg·mL-1),meanwile cell proliferation(at 25.0-50.0 μg·mL-1)was attenuated.VnA also showed a concentration-dependent inhibition of MMP2 and MMP9 production(at 3.1-50.0 μg·mL-1).Conclusions VnA has anti-metastatic protential by decreasing invasiveness of cancer cells as one of its anti-tumor pharmacological effects.
2008年S1期 v.25 13页 [查看摘要][在线阅读][下载 8K] [下载次数：19 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：55 ] Phase Ⅰ of clinical trials is the first stage of clinical pharmacology and body safety evaluation,including body tolerance test and pharmacokinetics test.The aim is providing evidence for dosage regimen and be the cornerstone of the preliminary assessment of efficacy and safety of phase Ⅱ of clinical trials.This text discussed the technique and requirement of phase Ⅰ of new drugs' clinical tolerance trials.
2008年S1期 v.25 14页 [查看摘要][在线阅读][下载 3K] [下载次数：18 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：62 ] -
Objective To discuss mechanism of BH3 domain counterpart BH3I-2' inducing colorectal cancer cell apoptosis.Methods Detected inhibition ratio and apoptosis of colorectal cancer cells HCT-116,which were treated by BH3I-2',with microplate reader and flow cytometry.Results Inhibition ratio of colorectal cancer cells,which were treated by BH3I-2',could reach about 50%.Ratio of viable apoptotic cell decreased and that of non-viable apoptotic cell increased as time went.Conclusions BH3I-2' can induce colorectal cancer cell apoptosis.
2008年S1期 v.25 15页 [查看摘要][在线阅读][下载 3K] [下载次数：16 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：44 ] Objective To discuss the role of clinical pharmacists in providing pharmaceutical care in pediatric respiratory department.Methods Supply pharmaceutical information,participate in clinical rounds,provide the rationalization proposal,help doctors to formulate correctly dose regimen,enhance medication efficiency;establish medicine record for the patient,record the drugs which were used,provide pharmaceutical care for the patient such as disease propaganda,medicine-use education,medicine consultation and so on.Results Promote rational administration,enhance the security of medical practice,the clinical pharmacists' work obtains the doctors' approval;improve the medication compliance,reduce patients' economy and spiritual burden,and obtain the patients' trust.Conclusions The pharmaceutical care carried out in pediatric respiratory department can help reduce the incidence of medication errors,cut down the medication cost,shorten the time of patients to be hospitalized,raise the medication efficiency,and promote the doctor-patient relationship harmoniously.In a word the clinical pharmacists are indispensable.
2008年S1期 v.25 16页 [查看摘要][在线阅读][下载 5K] [下载次数：47 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：55 ] - 亓佳;杨静玉;王芳;吴春福;
目的系统了解甲基苯丙胺的神经毒性,深入研究精神依赖性,从而为防治其滥用提供文献基础。方法综述近年来发表的国内外文献41篇。结果与结论随着药理学,分子生物学的快速发展,甲基苯丙胺的中枢毒性作用及其精神依赖性研究日益深入,但是对其滥用的防治仍然是一项艰巨的任务。
2008年S1期 v.25 17-22页 [查看摘要][在线阅读][下载 58K] [下载次数：1560 ] |[网刊下载次数：0 ] |[引用频次：24 ] |[阅读次数：115 ] - 孙明立;魏敏杰;金万宝;
随着现代分子生物学的迅速发展及其在免疫学研究中的广泛应用,人们已发现多种信号转导通路与免疫调节相关。目前研究较多的主要有TLRs信号通路、JAK-STAT信号通路、T细胞活化通路、B细胞活化通路等。这些信号转导通路任何环节发生异常均会导致疾病发生。
2008年S1期 v.25 23-26页 [查看摘要][在线阅读][下载 39K] [下载次数：685 ] |[网刊下载次数：0 ] |[引用频次：5 ] |[阅读次数：106 ] - 王莹;纪雪飞;邹莉波;
目的阿尔茨海默病(Alzhei mer's disease,AD)动物模型的研究,对本病的防治具有重要意义。方法综述近年来发表的国内外文献33篇。结果与方法本文综述了AD的动物模型近几年的研究成果,从(淀粉样蛋白、胆碱能损伤和转基因动物等几个方面讨论并比较这些动物模型在复制AD病理和行为改变方面的优点和不足。
2008年S1期 v.25 27-31页 [查看摘要][在线阅读][下载 47K] [下载次数：789 ] |[网刊下载次数：0 ] |[引用频次：5 ] |[阅读次数：172 ] - 郭磊;杨静玉;王芳;吴春福;
目的综述葡萄籽提取物的主要化学成分及药理活性的最新研究进展。方法查阅近年来的国内外相关文献,并进行归纳总结。结果发现葡萄籽提取物包括多酚类、脂质类及其他化学成分,具有抗氧化作用、心血管保护作用、抗肿瘤作用、抗辐射作用及其他药理学活性。结论葡萄籽提取物是一种很有开发价值的天然植物药。
2008年S1期 v.25 32-34页 [查看摘要][在线阅读][下载 28K] [下载次数：1227 ] |[网刊下载次数：0 ] |[引用频次：15 ] |[阅读次数：148 ] - 白雪峰;狄安稞;魏敏杰;
Synaptotagmins(syt)是一类以含有单个跨膜片段与两个保守C2区域为特征的蛋白家族,到目前为止,在脊椎动物共发现有16个成员。其中sytⅠ作为一种钙离子传感器介导神经递质囊泡的快速胞吐,SytⅦ分布较为广泛,在神经细胞,神经内分泌细胞,内分泌细胞,以及免疫细胞中均有分布,本文就其在不同组织细胞中的作用作一简要综述。
2008年S1期 v.25 35-40页 [查看摘要][在线阅读][下载 60K] [下载次数：179 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：74 ] - 高玲焕;邹莉波;迟天燕;
阿尔茨海默病(Alzhei mer's disease,AD)是一种中枢神经系统原发性退行性病变,是老年痴呆中最常见的类型。其特征性病理变化之一是患者脑内的神经炎性斑(老年斑),主要成分为细胞外β淀粉样蛋白(amyloid proteinβ,Aβ)的沉积,而Aβ又由淀粉样前体蛋白(amyloid precursor protein,APP)经序列水解而来。方法本综述主要叙述Aβ的产生、神经毒性、β淀粉样蛋白以及β淀粉样蛋白级联假说的部分新近研究进展。
2008年S1期 v.25 41-45页 [查看摘要][在线阅读][下载 43K] [下载次数：2439 ] |[网刊下载次数：0 ] |[引用频次：33 ] |[阅读次数：141 ] - 于兆进;任婕;魏敏杰;
乳腺癌是女性最常见的癌症,乳腺癌易感基因1(BRCA1)是研究比较深入的乳腺癌的抑癌基因。BRCA1基因失活,将会促进乳腺癌的发生。目前的研究成果比较倾向于认为:BRCA1基因突变与遗传性乳腺癌关系比较密切,基因突变位点多种多样,不同种族间各异;而在散发性乳腺癌中,启动子甲基化是BRCA1基因失活的主要方式,并且与散发性乳腺癌的病理学、免疫学及临床特征等参数间存在相关性。
2008年S1期 v.25 46-50页 [查看摘要][在线阅读][下载 56K] [下载次数：329 ] |[网刊下载次数：0 ] |[引用频次：2 ] |[阅读次数：95 ] - 孟雪莲;杨静玉;吴春福;
目的综述白藜芦醇的药理学进展。方法综述近年来发表的29篇文献。结果与结论白藜芦醇是一种天然的多酚化合物,存在于葡萄等多种植物中,被认为是一种植物抗毒素。研究表明,白藜醇具有抗肿瘤、心血管保护、抗炎等多种生物药理学活性。
2008年S1期 v.25 51-54页 [查看摘要][在线阅读][下载 40K] [下载次数：893 ] |[网刊下载次数：0 ] |[引用频次：41 ] |[阅读次数：122 ] -
Objective Our previous studies showed that the neuroprotective effect of pranlukast,a cysteinyl leukotriene receptor-1(CysLT1)antagonist,on global cerebral ischemia in rats.This study was performed to evaluate dose-and time-dependent properties of pranlukast on CA1 neuron loss following transient global ischemia in rats.Methods Brain injury was induced by an improved four-vessel occlusion(4-VO)in rats.pranlukast(0.03-0.30 mg·kg-1)was injected intraperitoneally either as multiple doses(before or after ischemia)or as a single dose(30 min before ischemia),respectively.Physiological variables were monitored and neuron count was measured by computer-assisted imaging.Results The 4-VO model produced continuing postischemic neuronal death in CA1 region.Administration of pranlukast(0.1 and 0.3 mg·kg-1,30 min before ischemia and 1,24,48 and 72 h after ischemia)markedly reduced CA1 death.Treatment with a single dose of pranlukast(0.1 mg·kg-1,30 min before ischemia)also resulted in a significant increase in the number of healthy CA1 neurons at 3 days.Of interest is the finding that pranlukast(0.1 mg·kg-1)rescued CA1 neurons from ischemic death even when treatment was delayed until 30 min or 1 h after ischemia.Conclusions The present study confirms pranlukast has a dose-and time-dependent cerebroprotective effects on CA1 neuron loss following transient global ischemia in rats,with an effective dose range of 0.1-0.3 mg·kg-1 and a therapeutic window of 1 h.These findings further support the therapeutic potential of CysLT1 receptor antagonists in the treatment of global cerebral ischemia.
2008年S1期 v.25 55页 [查看摘要][在线阅读][下载 11K] [下载次数：20 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：53 ] Objective To investigate the effects of acute and chronic administration of the non-competitive NMDA receptor antagonists MK-801 on c-Fos protein expression in different brain regions of mice and an-tagonistic action of clozapine.Methods Immunohistochemistry was used to detect the expression of c-Fos protein.Results MK-801(0.6 mg·kg-1)acute administration produced a significant increase in the expression of c-Fos protein in the layers Ⅲ-Ⅳ of posterior cingulate and retrosplenial(PC/RS)cortex,which was consistent with the previous reports.Moreover,we presented a new finding that MK-801(0.6 mg·kg-1)chronic administration for 8 days produced a significant increase of c-Fos protein expression in the PC/RS cortex,prefrontal cortex(PFC)and hypothalamus of mice.Among that,c-Fos protein expression in the PC/RS cortex of mice was most significant.Compared acute administration with chronic administration,we found that MK-801 chronic administration significantly increased the expression of c-Fos protein in the PC/RS cortex,PFC and hypothalamus.Furthermore,pretreatment of mice with clozapine significantly decreased the expression of c-Fos protein induced by MK-801 acute and chronic administration.Conclusions Marked expression of c-Fos protein induced by MK-801 is associated with neurotransmitters' change noted in our previous studies,and c-Fos protein,the marker of neuronal activation,might play an important role in the chronic pathophysiological process of schizophrenic model induced by NMDA receptor antagonist.
2008年S1期 v.25 55-56页 [查看摘要][在线阅读][下载 24K] [下载次数：35 ] |[网刊下载次数：0 ] |[引用频次：1 ] |[阅读次数：45 ] -
Objective To outline the recent progress in drug discovery for medication-induced dyskinesia(Parkinson disease,PD)and tardive diskinesia(schizophrenia)with emphasizing the role of 5-HT1A receptor.Methods Development of extrapyramidal syndrome(EPS)followed either chronic L-DOPA administration in PD(L-DOPA-induced dyskinesia,LID)or antipsychotic treatment in schizophrenia(Tardive dyskinesia,TD)remains a challenge in the clinical practice and drug discovery.In addition to the abnormal dopamine activity in the nigrostrial area that contributes to the LID or TD,recent information indicates that 5-HT1A receptor also plays an important role which is merging as promising target in treatment of LID or TD.Results l-Stepholidine(l-SPD),isolated from the Chinese herb Stephania,is known as a dual dopamine receptor agent(D1 receptor agonistic and D2 antagonistic activity).In addition,we further demonstrated that l-SPD binds to 5-HT1A receptor and exhibits a partial agonistic activity.In LID rat model,l-SPD not only attenuated the development of L-DOPA-induced dyskinesia(LID),but also relived the established LID.The effect of l-SPD on LID was completely blocked by pretreatment of 5-HT1A receptor antagonist,indicating the role of 5-HT1A receptor.Furthermore,we designed and synthesis a dual dopamine/5-HT1A receptor agonist MCL-135,which also exhibits a significant relief on LID while elicits its antiparkinsonian action.Conclusions 5-HT1A receptor plys an important role in the development of LID,targeted to dual dopamine/5-HT receptor may represent a promising strategy for drug design and discovery in LID and TD treatment.
2008年S1期 v.25 56页 [查看摘要][在线阅读][下载 13K] [下载次数：33 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：70 ] Objective To comparatively study anti-free radical and cytoprotective effects of quercetin(Q)and its monoglucoside isoquercetin(I),diglucoside rutin(R),which differs only in glycosyl-substitution at C-3 position of the molecules,using anoxia/hypoglycemia-induced cell injury model and thereby to explore the structure-effect relationship thereto.Methods The cell injury model was established by HEK293 cells cultured in vitro with Na2S2O3 plus sugar-free Earle's fluid as incubation medium.Cell survival rate(CSR),total antioxidant capacity(TAC),SOD and LDH levels were determined.The effect intensity of the 3 flavonoids was compared by means of IC50,the concentration required to achieve 50% inhibition of the changes in the above indices in injured cells.Results Q,I and R all concentration-dependently elevated CSR,TAC and SOD and reduced LDH level.The all of IC50s for the above indices were ranked in order of IC50,Q<IC50,I<IC50,R,namely,the effect intensity should be Q>I >R.Conclusions The 3 structurally similar flavoloids all have significant and concentration-dependent anti-free radical and cyto-protective effects with the intensity being in order of aglycone>monoglucoside>diglucoside;the substitution of-OH by sugar group at C-3 position of flavoloids and increase in the sugar-substituent number are associated with the effect intensity reduced;namely,the intensity of these effects of flavonoids is negatively related the substutution by sugar group at C-3 position.
2008年S1期 v.25 57页 [查看摘要][在线阅读][下载 10K] [下载次数：24 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：48 ] -
Objective To study the preventive effect of rosiglitazone glial activation,oxidative/nitrative stress and spatial memory deficits induced by intracerebroventricular(ICV)injection of streptozotocin(STZ)in rats.Methods 24 male Wistar rats were randomly divided into sham operated group,model group and rosiglitazone group.The model of Alzheimer's was induced by injection with ICV 10% STZ bilaterally,on day 1 and 3(3 mg·kg-1).The rats were treated with rosiglitazone(2 mg·kg-1,p.o.)for a consecutive 21 days,once a day,beginning 7 days prior to STZ injection.The learning and memory behavior was assessed using Morris water maze task and Y-maze 21 d after ICV STZ injection.Malondialdehyde(MDA),superoxide dismutase(SOD),glutathione(GSH)levels and nitrotyrosine immunoreactivity in brain were estimated as parameters of oxidative/nitrative stress.Brain acetyl cholinesterase(AchE)activity was measured by EllMann's method and activated microglia and astrocytes were detected by immunohistochemistry.Results ICV STZ injection resulted in a severe deficit in spatial learning and memory associated with increased MDA level(+69.5%)and nitrotyrosine immunoreactivity(+23.7%),decreased SOD activity(-29.2%)and GSH(-25.1%)in brain.It also showed the activated microglia and astrocytes in the cortex and hippocampal CA1 region and a significant decrease in acetylcholinesterase activity(-40.2%).Compared with model group,chronic administration of rosiglitazone significantly shorten the escape latency time from the third day in place navigation test,increase the number of passing through primary flat place in spatial probe test in Morris water maze test,and decrease the error times in Y-maze test(P<0.05 or P<0.01).In addition,it also prevented the glial changes,decreased the elevated MDA and nitrite levels and restored the depleted GSH and acetylcholinesterase activity in cortex(P<0.05),but had no effect on SOD activity in cortex.Conclusions Rosiglitazone has a neuroprotective role against streptozotocin-induced cognitive impairment and associated oxidative/nitrative stress.
2008年S1期 v.25 57-58页 [查看摘要][在线阅读][下载 24K] [下载次数：33 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：77 ] Objective In this study we will investigate the effect and possible mechanism of agmatine on MMP expression.Methods We established a transfection of human ADC gene into the murine bEnd.3 cells(bEnd.3-ADC)by the retroviral packaging cell line PT67.The bEnd.3-ADC cells were maintained in the hypoxia chamber for 6 hours,then returned to a normoxic incubator with glucose for 16 hours.We performed RT-PCR and western blot analysis against MMP-2,MMP-9,eNOS and ATF3,and measured the production of NO using Griess reagent.To determine the possible mechanism of agmatine on MMP expression we used inhibitory study.Results The expression of MMP was decreased by agmatine administered exogenously and endogenously,while eNOS was increased.We showed L-NAME(NOS inhibitor)altered the suppression of MMP-9 by exogenously administered agmatine.It seems that MMP-9 suppression by exogenously administrated agmatine is mediated,at least in part,via eNOS.We also found that ATF3 was increased significantly in ADC overexpression cells,but it was attenuated by NOS inhibitor.Furthermore,we found the suppression of MMP by agmatine was attenuated in cells transfected with ATF3 siRNA.Conclusions Our study suggested that endogenously administered agmatine suppress the MMP-2 and MMP-9 expression via eNOS-ATF3-MMPs pathway.
2008年S1期 v.25 58-59页 [查看摘要][在线阅读][下载 19K] [下载次数：28 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：60 ] - 陈福军;何苗;赵琳;姚维凡;赵海山;魏敏杰;
目的研究(-)表没食子儿茶素没食子酸酯在D-半乳糖所致痴呆小鼠体内的抗氧化作用。方法通过给小鼠皮下注射D-半乳糖(150mg·kg-1)的方法,每天一次,连续注射六周,以制备痴呆小鼠模型。两周后,用(-)表没食子儿茶素没食子酸酯(2mg·kg-1或6mg·kg-1)对模型小鼠灌胃四周治疗。通过进行水迷宫与避暗实验观察(-)表没食子儿茶素没食子酸酯对D-半乳糖所致痴呆小鼠的学习与记忆力的影响。通过对生化指标检测观察(-)表没食子儿茶素没食子酸酯对D-半乳糖所致痴呆小鼠海马的超氧化物歧化酶与谷胱甘肽过氧化物酶活性及丙二醛的含量的影响。结果皮下注射D-半乳糖削弱了小鼠的记忆及学习能力,使D-半乳糖所致痴呆小鼠海马中超氧化物歧化酶与谷胱甘肽过氧化物酶活性下降和丙二醛含量增加。灌胃给予(-)表没食子儿茶素没食子酸酯(2mg·kg-1或6mg·kg-1)明显的改善了小鼠的认知能力,提高了D-半乳糖所致痴呆小鼠海马中超氧化物歧化酶与谷胱甘肽过氧化物酶活性,减少了丙二醛的含量。结论(-)表没食子儿茶素没食子酸酯对D-半乳糖所致痴呆小鼠发挥了一定的抗氧化作用。
2008年S1期 v.25 59页 [查看摘要][在线阅读][下载 6K] [下载次数：202 ] |[网刊下载次数：0 ] |[引用频次：4 ] |[阅读次数：141 ] - 赵琳;何苗;金万宝;赵海山;姚维凡;魏敏杰;
目的观察维生素E对阿尔茨海默病(AD)模型小鼠学习记忆能力的改善作用及其机制。方法采用D-gal与NaNO2联合腹腔注射方法建立AD模型小鼠,在造模同时及模型建立后两个时间点灌胃给予维生素E(28,280IU.kg-1)观察疗效,实验结束后水迷宫检测各组小鼠的逃避潜伏期的变化,化学比色法检测脑组织AChE、SOD活性、MDA含量;免疫组织化学方法检测大脑皮层Aβ、NF-κB表达的变化。结果造模同时给予维生素E可使D-gal与NaNO2联合诱导的AD模型鼠的逃避潜伏期缩短([F(3,56)=6.959]onday1;[F(3,56)=6.689]onday2;[F(3,56)=17.379]onday3;[F(3,56)=13.391]onday4;P<0.05),AChE活性降低([F(3,28)=29.431],P<0.05),SOD活性提高([F(3,28)=7.372],P<0.05),MDA含量降低([F(3,28)=11.235],P<0.05);同时可明显降低AD模型鼠脑组织中Aβ、NF-κB的表达(P<0.05)。模型建立后给予维生素E未发现上述变化。结论维生素E可预防化学诱导的AD模型小鼠学习记忆能力损伤,可能机制与提高SOD活性、降低MDA含量、降低AChE活性、降低脑组织中Aβ、NF-κB的表达等相关。
2008年S1期 v.25 59页 [查看摘要][在线阅读][下载 6K] [下载次数：216 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：102 ] - 唐秋实;李莉;周平;刘慧慧;时利德;蔡原;
目的采用慢性铝暴露大鼠模型来研究铝暴露对谷氨酸介导的神经传递的影响,进而从递质释放角度阐明在此阶段中铝影响LTP的机制。方法成年Wistar大鼠按体重随机分为3组,分别自由饮用:蒸馏水(对照组),0.2%AlCl3水溶液,0.4%AlCl3水溶液,染毒3个月后测定各项指标。结果随铝暴露剂量增大,大鼠海马齿状回群体峰电位幅值增强率逐渐减小,并呈剂量依赖性。免疫组化结果显示与对照组相比,铝暴露组的谷氨酸活性受到明显抑制,并且随着暴露剂量增大,谷氨酸活性降低,呈剂量依赖性。结论慢性铝暴露可损害成年大鼠海马LTP的诱导与维持,这可能与大鼠海马中谷氨酸的活性降低有关,对正常的学习记忆过程产生不利影响。
2008年S1期 v.25 60页 [查看摘要][在线阅读][下载 6K] [下载次数：118 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：82 ] - 何苗;赵琳;姚维凡;赵海山;陈福军;魏敏杰;
目的研究(-)表没食子儿茶素没食子酸酯对D-半乳糖诱导的阿尔茨海默病小鼠的抗凋亡作用。方法给小鼠每日按150mg·kg-1皮下注射D-半乳糖一次,连续注射6周,以制备阿尔茨海默病小鼠模型,造模2周后,给EGCG低剂量和高剂量治疗组小鼠每日分别按2mg·kg-1和6mg·kg-1灌胃给予EGCG一次,连续给药4周。通过HE染色、TUNEL染色、免疫组化和Western blot印迹分析等方法观察EGCG对D-半乳糖诱导的阿尔茨海默病小鼠脑内神经元凋亡情况及海马区促凋亡蛋白caspase-3的活性及表达。结果给小鼠连续皮下注射D-半乳糖明显的增加了神经元细胞凋亡指数(P<0.01),并提高了小鼠海马区caspase-3的活性及表达(P<0.05);EGCG(2mg·kg-1和6mg·kg-1)明显的降低了D-半乳糖诱导的阿尔茨海默病小鼠神经元细胞的凋亡指数(P<0.01),并降低了小鼠海马区caspase-3的活性及表达(P<0.05)。结论EGCG通过抑制D-半乳糖诱导的阿尔茨海默病小鼠海马区caspase-3的活性及表达,发挥有效的抗凋亡作用。
2008年S1期 v.25 60页 [查看摘要][在线阅读][下载 6K] [下载次数：270 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：131 ] -
Objective To investigate the improvement of Xanthoceraside on learning and memory impairment in mice induced by intracerebroventricular injection of Aβ1-42(i.c.v.Aβ1-42)and the possible mechanisms of its protection against AD.Methods Y-maze test,water-maze test and step-down test were used to investigate the learning and memory ability of mice;Biochemical analysis was used to detect the activity of CAT,T-AOC,ATPase and the content of MDA.Results The results showed that Xanthoceraside could significantly increase the alternation behavior in Y-maze test,shorten swimming time in water maze test and increase the latency and decrease the number of errors and the total time of shock in step-down test.Xanthoceraside markedly increased the activity of CAT,T-AOC,ATPase,at the same time,decreased the content of MDA.Conclusions Xanthoceraside can improve learning and memory impairment in mice induced by i.c.v.Aβ1-42 significantly.The mechanism may be associated with the protection against damage induced by free radicals;the inhibition of membrane lipid peroxidation and the improvement of metabolism of brain.
2008年S1期 v.25 60-61页 [查看摘要][在线阅读][下载 18K] [下载次数：39 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：865 ] Objective To investigate the protective effect of Xanthoceraside on various injured PC12 cells models and to indicate the mechanism of Xanthoceraside therapying dementia.Methods Four injured PC12 models induced by glutamate,hydrosulfurous sodium,sodium nitroprusside and potassium chloride accordingly were used to assay the effect of Xanthoceraside on PC12 cells by using morphological examination and MTT assay.In addition,in the model of glutamate injury,the Lactate dehydrogenase(LDH)and the lipid peroxidation products malondialdehyde(MDA)were measured by a spectrophotometric method,reactive oxygen species(ROS)generation were measured with flow cytometry.Results It was found that Xanthoceraside could obviously increase the viability of PC12 cells injured by four injury models.Xanthoceraside could also decerase the levels of LDH release,MDA production,and ROS generation induced by glutamate.Conclusions These data indicate that Xanthoceraside may provide a useful therapeutic strategy for the treatment of progressive neurodegenerative diseases such as Alzheimer's disease(AD).
2008年S1期 v.25 61页 [查看摘要][在线阅读][下载 11K] [下载次数：30 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：77 ] -
Objective The effect of the ephedra/ephedrine alkaloid methylephedrine(dl-methylephedrine hydrochloride for testing in this paper)on cognitive related synaptic plasticity was investigated by recording extracellular field evoked potentials and its LTP in hippocampal dentate granule cells in urethane-anaesthetized rats in vivo.Methods Single pathway recording of evoked field potentials was made from the dentate granule cells of hippocampal hemisphere in response to stimulation of the ipsilateral medial perforant path(MPP).Two parameters,the amplitude of population spike(PS amplitude)and the latency of the PS,were employed to evaluate the effects of drug on the overall changes in cellular responses.Results The present study show that methylephedrine 90 mg·kg-1 intraperitoneally,about 1/3 LD50,could increase the latency of the PS in hippocampal dentate granule cells by constant single stimulation of the MPP as the basal ransportation.However,the 30 mg·kg-1 and 10 mg·kg-1 dosage had no effect on the latency,and there are no influences of PS amplitude for all examinational groups.The methylephedrine 90 mg·kg-1 group significant enhanced the development of amplitude LTP in hippocampal dentate granule cells that induced by 60 Hz,60 pulses conditional tetanus in medial perforant path area.Also,the 30 mg·kg-1 group can promoted the maintenance of LTP induced by this tetanus,but no promotion on PS amplitude LTP appeared in this dosage and no any changes been found in 10 mg·kg-1 dosage group.Conclusions The ephedra/ephedrine alkaloid methylephedrine can modulate the synaptic plasticity in the lateral perforant path.A possible mechanism of methylephedrine on hippocampal LTP is been discussed.
2008年S1期 v.25 62页 [查看摘要][在线阅读][下载 8K] [下载次数：42 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：77 ] - 唐宏涛;魏敏杰;
目的研究FANCF基因沉默对乳腺癌MCF-7细胞生物学特性的影响,并检测相关指标的变化,探讨FANCF基因是否参与乳腺癌的发生、发展及耐药性的形成。方法构建FANCF-shRNA质粒,转染FANCF-shRNA使乳腺癌MCF-7细胞FANCF基因沉默;MTT法检测FANCF基因沉默对MCF-7细胞增殖的影响;流式细胞仪PI单染法及AnnexinV-FITC/PI双染法检测FANCF基因沉默对MCF-7细胞周期及凋亡的影响;RT-PCR检测FANCF基因沉默前后耐药相关基因mRNA表达水平的变化。结果成功构建FANCF-shRNA质粒,RT-PCR验证转染FANCF-shRNA后48h出现FANCF基因沉默;与阴性对照组相比,FANCF基因沉默后,MCF-7细胞增殖明显受到抑制,转染FANCF-shRNA后48h和72h的抑制率分别为12.65%±1.24%和29.64%±0.87%(P<0.05);S期MCF-7细胞比率增加(33.38%±0.68%,P<0.05),细胞周期阻滞在S期;转染FANCF-shRNA后MCF-7细胞凋亡率明显增加,转染后48h和72h的凋亡率分别为28.95%±1.81%和49.00%±2.32%(P<0.05);P-gp、BCRPmRNA表达水平降低,MRP、LRPmRNA表达水平无明显变化(P>0.05)。结论FANCF基因沉默可抑制人乳腺癌MCF-7细胞增殖,促进细胞凋亡,并使细胞周期阻滞于S期;并可抑制BCRP等耐药相关基因的mRNA表达,参与乳腺癌细胞耐药性的调控。
2008年S1期 v.25 63页 [查看摘要][在线阅读][下载 7K] [下载次数：100 ] |[网刊下载次数：0 ] |[引用频次：2 ] |[阅读次数：139 ] - 任婕;王麟;金锋;米小轶;魏敏杰;
目的分析乳腺癌易感基因(BRCA1)和相关凋亡调控蛋白C-myc、Bcl-2和p53在乳腺浸润性导管癌中表达的相关性,与临床病理指标的关系,探讨BRCA1等蛋白表达检测对乳腺癌诊断和治疗的指导意义。方法免疫组织化学SP法,检测20例乳腺良性病变和120例乳腺浸润性导管癌中BRCA1、C-myc、Bcl-2和p53的表达,收集患者临床资料,通过校正的Pearsonχ2检验进行统计分析。结果在良性乳腺病变,BRCA1、C-myc和p53蛋白在细胞核的阳性表达率分别为95.0%(19/20)、10.0%(2/20)和5.0%(1/20),Bcl-2在细胞质/膜阳性表达率为85.0%(17/20);在浸润性导管癌,BR-CA1、C-myc和p53蛋白阳性表达率分别为60.0%(72/120)、38.3%(46/120)和36.7(44/120),Bcl-2阳性表达率为50.8%(61/120);与良性乳腺病变比较,浸润性导管癌中BRCA1、Bcl-2阳性表达率明显降低,C-myc和p53表达增加,均有显著性差异(P<0.05)。BRCA1表达与C-myc和p53过表达相关;C-myc表达与p53表达相关;BRCA1、p53、C-myc表达与Bcl-2表达均无显著相关性。BRCA1、C-myc和Bcl-2表达与组织分级和腋淋巴结转移相关。结论乳腺浸润性导管癌中,BRCA1失表达与C-myc和p53过表达、组织学分级和腋淋巴结转移相关,凋亡调控基因的异常表达参与乳腺浸润性导管癌的发生。
2008年S1期 v.25 63页 [查看摘要][在线阅读][下载 7K] [下载次数：171 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：84 ] - 任婕;魏敏杰;金锋;赵海山;姚维范;冯婉玉;
目的通过本研究分析影响BRCA1蛋白表达的因素;BRCA1蛋白表达与临床相关指标的相关性。方法检测121例散发性乳腺癌和20例乳腺良性组织石蜡标本的BRCA1蛋白表达,结合ER、HER-2的表达情况和患者的年龄、原发肿瘤的病理类型和腋淋巴结转移状况,进行统计学分析。结果20例乳腺良性组织BRCA1蛋白均在细胞核阳性表达;121例散发性乳腺癌组织按ER和HER-2的表达情况分组后,在ER(+)HER-2(+)、ER(-)HER-2(+)、ER(+)HER-2(-)、ER(-)HER-2(-)各组中,BRCA1蛋白在细胞核阳性表达率分别为37.0%(10/27)、37.5%(6/16)、74.4%(32/43)、65.7%(23/35),乳腺癌ER(-)HER-2(+)与ER(+)HER-2(-)和ER(-)HER-2(-)组间的BRCA1蛋白表达有显著性差异(P<0.05);ER(+)HER-2(+)与ER(+)HER-2(-)组间的BRCA1蛋白表达也有显著性差异(P<0.05)。结果表明,乳腺癌组织中HER-2阳性表达的,BRCA1阳性表达率降低;BRCA1蛋白低表达、HER-2高表达的乳腺癌组织,腋淋巴结转移的比例增高;BRCA1蛋白表达在不同病理类型的乳腺癌中未见差异。结论BRCA1蛋白表达检测,结合ER、HER-2的表达水平,对临床判断预后有指导意义。
2008年S1期 v.25 64页 [查看摘要][在线阅读][下载 7K] [下载次数：83 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：74 ] - 刘淼;魏敏杰;赵福杰;
目的研究shRNA表达质粒稳定转染,靶向沉默HER-2/neu基因对子宫内膜癌细胞株Ishikawa细胞增殖及其对孕激素敏感性的影响。方法根据HER-2/neumRNA的序列设计和合成两条shRNA.分别将其与质粒(pSilencer4.1CMV neo,Ambion)连接,并将连接好的质粒通过LipofectamineTM2000(invitrogen)转染Ishikawa细胞株。应用含有250μg·mL-1G418的DMEM培养基筛选稳定转染克隆。用RT-PCR法及Western blot分别检测稳定转染细胞HER-2/neumRNA及p185蛋白表达水平,用Annexin-V检测细胞凋亡率。用10μg.μL-1孕激素培养细胞72小时后,用MTT法分别检测转染细胞及未转染细胞的增殖率。结果转染特异性shRNA表达质粒组Ishikawa细胞HER-2/neumRNA及p185蛋白表达水平明显低于对照组细胞。细胞增殖率明显降低而细胞凋亡率明显增高(P<0.05)。用10μg.μL-1孕酮培养细胞72小时后,转染特异性shRNA的细胞组细胞增殖率明显低于未转染细胞组(P<0.05)。结论RNA干扰可以明显降低Ishikawa细胞株HER-2/neumRNA及185蛋白的表达,从而抑制细胞增殖并诱导细胞凋亡。HER-2shRNA还可以增加Ishikawa细胞株对孕激素的敏感性,与孕激素存在协同效应。
2008年S1期 v.25 64页 [查看摘要][在线阅读][下载 7K] [下载次数：98 ] |[网刊下载次数：0 ] |[引用频次：2 ] |[阅读次数：120 ] - 张依宁;张惠晶;魏敏杰;孙明军;
目的Wnt通路与TGF-β通路分别在大肠癌细胞粘附中发挥重要作用,但两通路间是否存在交叉调控尚不明确,本实验的目的即是阐明大肠癌中Wnt通路和TGF-β通路交叉调控作用与机制。方法人类大肠腺癌细胞株HCT116/HT29(中国科学院典型培养物保藏委员会细胞库,上海)分别经携带APC-shRNA及Smad4-RNA序列的质粒(Psilencer4.1neo,Ambion)转染后,应用RNA干扰技术建立APC基因沉默、Smad4基因沉默和双基因沉默细胞系。然后应用反转录-PCR和western-blot比较每个细胞系粘附因子E-cadherin、catenins和转录因子c-myc/CyclinD1/P21/Met等在细胞中分布与表达差异上的变化。结果在APC-shRNA克隆大肠癌细胞株(APC基因沉默),TGF-β可明显抑制其过快生长速度,但丧失了诱导α、β、γ-catenin和E-cadherin表达增加作用。在对照组与沉默组间,E-cadherin/catenins/c-myc/CyclinD1/P21/Met的分布与表达存在显著性差异(P<0.05)。结论Wnt信号传导通路在正常细胞中是关闭的,但在结直肠癌细胞中被激活。TGF-β是一种多向细胞调控因子,它在肿瘤发生的早期发挥抑癌作用,但在进展期则促进肿瘤细胞的转移。TGF-β促进cadherins表达依赖于APC活性,说明Wnt通路和TGF-β通路均以APC作为共同的调控因子在大肠癌细胞粘附与生长中发挥相互调控作用。
2008年S1期 v.25 65页 [查看摘要][在线阅读][下载 7K] [下载次数：286 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：93 ] - 于兆进;任婕;马文锋;姚维凡;魏敏杰;
目的检测BRCA1和CEP17在BRCA1启动子甲基化和非甲基化的散发性乳腺癌中的基因拷贝数。方法按照BRCA1启动子甲基化状态将46例散发性乳腺癌分成甲基化组和非甲基化组。在由冰冻病理组织制作的组织印片上,应用双色荧光原位杂交(FISH)技术检测BRCA1和CEP17的基因拷贝数。本实验室自行PCR扩增BRCA1探针并标记生物素(Biotin ULS Labeling Kit,Fermentas Company);PCR扩增CEP17探针并标记CyTM3(Label IT Cy3TMLabelingKit,Mirus Bio Corporation)。探针的杂交效率通过对正常白细胞进行BRCA1/CEP17FISH来检测。结果在BRCA1启动子甲基化的乳腺癌组织中BRCA1和CEP17的平均基因拷贝数分别为1.70和1.77,而在非甲基化的组织中分别为2.25和2.33。两组间的BRCA1(P<0.001)和CEP17(P<0.005)基因平均拷贝数存在明显差异。但总体的BRCA1/CEP17比率没有显著不同(甲基化组平均为0.96,非甲基化组为0.97,P=0.32)。结论我们在中国乳腺癌群体中建立了FISH检测方法,并发现BRCA1基因拷贝数与启动子甲基化相关。
2008年S1期 v.25 65页 [查看摘要][在线阅读][下载 7K] [下载次数：133 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：120 ] Objective To study the effect of saponins of asparagus on apoptosis and the variations of caspase8,caspase-9 and caspase-3 activity in the process of asparagus induced apoptosis in HepG-2,to investigate the apoptosis mechanism further.Methods Asparagus on apoptosis effects on tumor cells cultured-HepG-2 with different concentrations at different time,IC50 value was measured by MTT assay,the apoptosis rate was determined by FCM with AnnexinV/PI staining,their apoptotic morphology were observed by electron microscopy and Colorimetric method was used to measure caspase-8,9 and caspase-3 activities.Results Experiments of antitumour in vivo showed that saponins of asparagus can inhibit the growth of tumor cell of HepG-2 in evidence,IC50 was 101.15 mg·L-1.Cultured for 72 h,the apoptosis rate had positive increased with concentrations.Apoptotic morphology was observed by electron microscopy.The activities of caspase-8,caspase-9 and caspase-3 had positive increased with concentrations.And have significant difference compared with negative control group(P<0.01).The activities of caspase-8 were high at 24 h,but the activities of caspase-9 and caspase-3 is high at 48 h.Conclusions Aaponins of asparagus can inhibit the growth of tumor cell of HepG2,and the underlying mechanism might be related to up regulation of caspase-8,9 activity which subsequently transforms caspase-3 into its active form.
2008年S1期 v.25 66-67页 [查看摘要][在线阅读][下载 22K] [下载次数：37 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：72 ] -
Objective BH3 domain protein plays an important role in control mechanism of cell apoptosis.The article mainly discusses its mechanism of promoting cell apoptosis and control.Methods The article analyzed and evaluated the mechanism of BH3 domain protein promoting cell apoptosis by internal and overseas literature.Results Activation of BH3 domain protein could promote the increase of mitochondrial membrane permeability,then it would start mitochondrial apoptosis pathway,and at the last the cell apoptosis.Conclusions BH3 domain protein is the necessary condition of starting cell apoptosis.Its activation can cause cell apoptosis.
2008年S1期 v.25 66页 [查看摘要][在线阅读][下载 10K] [下载次数：43 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：34 ] Apoptosis is one of the main types of programmed cell deaths(PCD)and involves a series of biochemical events that lead to a variety of morphological changes and death.The initial and progress of apoptosis is precisely regulated.This review will summarize current knowledge of the signal transduction pathways of apoptosis.It is now well-established that the apoptotic signals generally involve the extrinsic or intrinsic pathways of apoptosis.The extrinsic pathway originates at the membrane and engages cell surface death receptors whereas the intrinsic pathway predominantly involves mitochondria.In the intrinsic pathway,the cell death signal induced changes of mitochondrial membrane permeability and the loss of membrane potential.Many proteins factors released,and then cytoplasmic cytochrome C and caspase-9 form of apoptosis.The activated caspase-9 cut caspase-3,then cell dead at last.In the case of extrinsic pathway,several death receptors exist including Fas,TNFR-1,DR3,DR4,DR5 and DR6.These death receptors contain an intracellular region of approximately 80 amino acids that is designated as "death domain".The death domain is an important structure that plays a key role in the transduction of apoptotic signals.The interaction between Fas and its ligand(FasL)triggers the formation of a death-inducing signaling complex(DISC),which subsequently recruits and activates caspase-8;this in turn activates other procaspases and culminates in the cleavage of cellular substrates and apoptosis.During the process of tumor cell lines apoptosis Inducted by chemotherapy.It is easy to see the increasing of the Fas receptors and inducing of FasL expression,it can inhibite apoptosis when the blocking Fas /FasL.Tumor necrosis factor(TNF)-related apoptosis-inducing ligand(TRAIL)is a type II transmembrane protein belonging to the TNF family of death ligands.TRAIL has been suggested as a safe and tumorselective anticancer agent with low toxicity to normal tissues,and is thought to play a role in tumor immune surveillance by NK,T cells and probably also cells of the innate immune system.The interaction between TNF and its ligand(TRAIL)recruits and activates caspases,TRAIL transmitting the signals through FADD,the probable mechanism is that:activated TRAIL combined with FADD through mutual recognition of Death domain,FADD combined MACH/FLICE(caspase-8),and then activates ICE/CED3 of caspase-8 and other proteins.The vast majority of cancer chemotherapy drug,mainly play a role through mitochondria-induced apoptosis pathway.TRAIL-induced apoptosis rely on the activation of caspase-8 and caspase-3.The mitochondrial membrane potential was reducted and the cytochrome C was released,leading to no damage of mitochondrial integrity after DNA cracking.Caspase is a specific type of acid cysteine protease,in apoptosis directly involved in the process of implementing the early start of apoptosis,signal transduction and apoptosis of late.Caspase-8 plays a key role in the death receptor-mediated apoptosis.
2008年S1期 v.25 67-68页 [查看摘要][在线阅读][下载 26K] [下载次数：44 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：56 ] -
Apoptosis,also known as programmed cell death,is the removal of damaged body organizations,aging or redundant cells in a suicide,has to maintain the health of the body,the normal development of the nervous system,the immune system to maintain the normal function of such areas is of great significance.The morphological characteristics of apoptosis are the cytoplasm concentrated,condensed nuclear chromatin,DNA fragments of a large-scale,the cell membrane invagination and foam formation of apoptotic bodies.There are two classic apoptosis ways which are generally accepted by majority of the scholars currently:Mitochondrial pathway and Death receptor pathway.Mitochondrial membrane is a two-tier structure surrounded the cystic,between the external cavity and internal cavity which is called the Room,surrounded by the internal cavity known as the mitochondria internal room or mitochondrial matrix.Mitochondria with the functions of control cell survival and death:mitochondria play an important role in physiological such as oxidative phosphorylation,electronic transfer,storage Ca2+,energy metabolism,anti-oxidation activity and so on,to provide the basic energy to the various activities of cell life.Study found that mitochondria contain some of the material is closely related to apoptosis,such as Cyt-C,Smac/Diablo,AIF,Ca2+,ROS and so on.In the signal to stimulate apoptosis,mitochondrial membrane permeability,resulting in a series of key changes,including Cyt-C,Smac/Diablo release,decline of the mitochondrial membrane potential(ψm),the state of the redox within cells,the intervention of Bcl gene family and so on.Different signal transduction ultimately focuses on the mitochondria to activate or inhibit these incidents,then the corresponding signal transduction to control apoptosis.Therefore,the mitochondria in the incidence of apoptosis play an important role.In recent years,the study confirmed that apoptosis imbalance can cause a variety of human diseases.And there is a close relationship among apoptosis and tumor occurrence,development and dissipated.The resistance to apoptosis caused by the disorders of tumor cell apoptosis control is one of the important reasons which cause tumor.Therefore,to prove the mechanisms of apoptosis in mitochondrial pathway and use these mechanisms to prevent and treat cancer is of great importance.
2008年S1期 v.25 67页 [查看摘要][在线阅读][下载 12K] [下载次数：44 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：46 ] Objective To explore the inhibition of juglone in Qinglongyi on A-549 cells in vitro.Methods MTT assay was used.Laser confocal scanning microscope was used to observe apoptotic morphology.Changes of cell cycle are studied by flow cytometry analysis.Results MTT assay showed that juglone had a marked growth inhibition in A-549 cells and the IC50 is respectively 3.4×10-5 mol·L-1,1.8×10-5 mol·L-1 and 2.6×10-6 mol·L-1 after treatment for 24,48 and 72 h by juglone.Through Laser confocal scanning microscope,we can see that juglone can induce the apoptosis.Cell cycle changes are analyzed by flow cytometry with cells at G1 phase significantly less than those of control and cells at G2 phase significantly more than those of control.Conclusions It suggests that juglone could apoptosis of A-549 cells with the cell cycle arrest on G2 phase in distinct dose-dependent manner.
2008年S1期 v.25 68-69页 [查看摘要][在线阅读][下载 25K] [下载次数：43 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：35 ] -
Objective To study the effect of Asparagus officinalis polysaccharide on the number and activity of erythrocyte complement receptor 1 in S180 mice.Methods Red blood cells from mice venous blood were labeled by rat anti-mouse CD35 monoclonal antibody and FITC-conjugated goat anti-mouse antibody.Using flow cytometry,we determined the number of ECR1.Using microscope,we studied the adherence between erythrocyte immunity and C3b receptor or tumor-cell by RBC-C3bRR and DTER.Results Comparing the mean value of the number of CR1 on each RBC of high and middle groups with control groups,the mean value of the number of CR1,RBC-C3bRR and DTER of Asparagus officinalis polysaccharide groups are increased significantly.Conclusions Asparagus officinalis polysaccharide can improve the erythrocyte function of S180 mice,which may be one of its most important antitumor mechanisms.
2008年S1期 v.25 69页 [查看摘要][在线阅读][下载 11K] [下载次数：31 ] |[网刊下载次数：0 ] |[引用频次：1 ] |[阅读次数：55 ] Ovarian cancer is one of the three malignant tumors in female reproductive system,the death rate locates in the first place of gynecological cancer.Most patients are already at the advanced stage when examine their bodies,five-year survival rate are only about 20% to 30%.So gynecological cancer has become one of tumor which the most waiting to be considered.It happens refer to the incidence of chromosomal abnormalities,cancer gene change.The inactivation of tumor suppressor gene,inhibitor of apoptosis and other genetic changes,the imbalance in the regulatory network due to the interaction of multiple genes and their product.Chromosomal abnormalities play an important role in the development of ovarian cancer,the chromosomes of common characteristic and non-random changes are 1,3,5,6,7,8,11,12,15,17,18,20,22 etc.Cancer gene including K-ras,c-erb-B2/HER-2,D1(CyclinD1),AIB1 etc.K-ras coded protein p21 is activated through point mutation,cause the enzyme activity deprivation of GMP,slowed down the speed of GTP degrdn into GMP,activate target molecule persistently,make cells proliferate persistently,then leading to cancer.HER-2 gene amplification result in the over expression of HER-2 protein,made cells over proliferate,Protein over expression convey the strong signal of proliferation,over activate the early transcription factor and certain gene in the nuclear,then promote the occurrence of cancer.Cyclin D1 promote cells enter from S to Gl phase,thus contribute to the proliferation of cell division,then canceration.AIB1 gene over express,will cause tumor cells immortalized.Tumor suppressor gene,such as BRCA1、p53、p73、p16 etc.The expression depl of BRCA1 protein in ovarian Cystadenocarcinoma prompt that the reduction of BRCA1 protein synthesis,resulting in apoptosis decreased,the cell proliferation disinhibit,then disorder and proliferate,thus leading to cancer.p53 mutation happened in about 30 percents to 80 percents of ovarian cancer patients.p73 play a role in the tumor neovascularization.In ovarian cancer,p16 deletion and the mutation rate over 50 percents.Regulating factor Apoptosis including bcl-2 gene family,Caspase family and Survivin.Bcl-2 play an important role in the occurrence of ovarian cancer,Bcl-2 gene family members can form into homodimer or hterodimer,play a part in promoting or inhibiting apoptosis respectively.The activation of caspase after the translation is correlate to apoptosis and necessary to apoptosis.The expression of apoptosis inhibitory factor Survivin in epithelial ovarian cancer were the increased In addition,cyclooxygenase-2(COX-2),protein kinase B(PKB),protein kinase C(PKC),telomerase and vascular permeability factor also closely related to the development of ovarian cancer.
2008年S1期 v.25 70-71页 [查看摘要][在线阅读][下载 26K] [下载次数：40 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：41 ] -
Objective To study on the mechanism of growth inhibiting and apoptosis inducing effect of total alkaloid in the CSEO(Capparis spinosa L.essential oil,CSEO)on human hepatocarcinoma cell Line HepG-2.Methods The growth inhibiting effect of the CSEO on human hepatocarcinoma cell Line HepG-2 was measured by MTT method.Morphological observation of the HepG-2 cells was completed by fluorescence microscope.The changing of mitochondrion membrane potential induced by CSEO was observed by staining with Rhodamine123.Effect of the CSEO on intracellular Ca2+ level of the HepG-2 cells was measured by laser confocal microscope.Results The CESO has obvious growth inhibiting effect on the HepG-2 and seems to be dose-dependent,and its IC50 is 127.5 μg·mL-1.The characteristic apoptosis morpha of HepG-2 cells has been observed,and the apoptosis percentage increase to 44.447% in the 300 μg·mL-1 dosage group.In addition,the progress of cells cycle of G1 period has been blocked,and the cellular proportion in S and G2 period is decreased in the 75 μg·mL-1 and 150 μg·mL-1 dosage groups by the function of CSEO for 48 h.The mitochondria membrane potential(Δψm)effected by CESO is decreased,while the curve moves toward left.In addition,the intracellular Ca2+ level is increased by the function of CESO in the middle and high dose groups.Conclusions The CESO has obviously growth inhibiting and apoptosis inducing effect on human hepatocarcinoma cell Line HepG-2 by the mechanism of decreasing the mitochondria membrane potential and increasing the intracellular Ca2+ level.
2008年S1期 v.25 70页 [查看摘要][在线阅读][下载 12K] [下载次数：23 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：34 ] Survivin was firstly separated in hybridization of Effector Cell Protease Receptor-1(EPR-1)cDNA in human genome by Yale University's Ambrosini in 1997,which is member of the inhibitor of apoptosis proteins(IAPS).Unlike other IAP protein,found during embryonic and fetal development,survivin wascompletely down-regulated and undetectable in normal adult tissues,and became prominentlyre expressed in all of the most common cancers.It through includes the cysteine/histidine rod-shaped viral IAP repetition sequence baculoviral IAP repeats(BIRs)the structure territory directly or intervenes Caspases the function to display indirectly its anti-perishes weakly the function,simultaneously it also is in the cell division process the chromosome traveler protein(chromosome passenger protein).There are three approaches by which survivin inhibits the processing of apoptosis:(1)inhibits processing of down stream effector caspase-3,caspase-7and caspase-9 in cell receiving apoptotic stimuls;(2)with the Smac/DIABLO function,sends the XIAP activeness to increase,XIAP through directly affects and restrains its function with caspases,achieved restrains function which perishes weakly;(3)through restrains p53 the function to block perishes weakly the process.Survivin expressed specificity and its function multiplicity.Survivin only expresses in tumor tissues and cannot be found in normal terminally differentiated tissues.This kind of expression is been extremely low the cell cycle strict regulation in the G1 time expression,the S time is G1 time 6 times,the G2/M time advances to 40 times,demonstrated its expression has the G2/M time dependence specificity.It has bi-function of inhibiting apoptosis and involving in cell cycle control.Survivin has found in most of tumor cells in recently researches.Survivin expresses generally in all tumor cell line in the American State-run Cancer Research institute anti-tumor medicine screening procedure 60 different tumor cells,in which expresses in the mammary gland cancer cell and the lung cancer cell highly,expresses in the kidney cancer lowly.Survivin except in tumor cell high expression,at breast cancer,tumor in front of and so on endometrium cancer,cervical cancer cancers in the pathological change has the expression.Survivin is over expressed in early malignant,which brokes the balance of proliferation and apoptotic,causes the occurrence of tumor.Obviously,survivin is closely related to the uncontrolled growth carcinogenesis,development and tumorigenesis.Because Survivin in tumor organization's special expression and perishes weakly in the suppression cell and adjusts in the cell division the vital role,causes it to become one to have the latent application value tumor designated object and the tumor treatment new target spot.The recent research of survivin in the development,treatment and situation of tumor is introduced.
2008年S1期 v.25 71-72页 [查看摘要][在线阅读][下载 29K] [下载次数：41 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：46 ] -
Pancreatic carcinoma is the most common pancreatic neoplasm characterized by latentmorbidit,poor prognosis,high mortality rate and limited choice of treatment.Quite a lot studies focused on its pathogenesis,and showed molecular genetic alterations,which derived of genetic and environmental factors and played an important role in tumorigenesis.Recently,more and more findings laid particular emphasis on the changes of gene molecule and some were confirmed in vitro and in vivo.In this paper,we made a review and summarized the arked molecular changes and signalings of the four pathways to understand their functions in Pancreatic carcinoma.The most important changes concentrate on K-RAS,p16 INK4a,P53 and SMAD4 gene,secondly,the changes of p14ARF,TGF-β,LKB1 /STK11,BRCA2 and growth factor Hedgehog and Notch path way and Telomere also play a important role in pancreatic carcinoma.The vast majority(83%)of pancreatic carcinomas had a distinctive genetic fingerprint,comprising activation of the K-ras oncogene and inactivation of the p16 gene,generally also accompanied by alterations in the p53 gene(in 76% of the tumors).The activation of K-ras appears nearly to be a prerequisite for the development of pancreatic carcinoma.Also,the binary alteration of K-ras and p16 is an extremely uncommon combination among other human tumor types.This particular genetic imprint of pancreatic carcinomas could have diagnostic utility in the evaluation of patients with metastatic adenocarcinoma of unknown primary origin.The evaluation of genetic alterations as they naturally occur in humantumors allows the formulation of hypotheses concerning the biological processes that involve human tumongenesis.A central tenet of tumori genesis,that positive selection is exerted upon those tumor cells that alterrate-limiting regulatory pathways,implies that mutation of one gene abrogates the need for inactivation of another gene in the same tumor suppressive pathway.It follows,therefore,from the genetic profile of pancreatic carcinoma that K-ras,p53,pi6,DPC4,and BRCA2 each belong to a distinct tumor-suppressive pathway.The concept of distinct tumor-suppressive pathways,however,should not exclude the possibility of cooperative interactions between the pathways.In this series,for example,DPC4gene inactivation was limited to tumors with genetic inactivation of the p16 gene.The involvement of the p13,p16,and DPC4 pathways in pancreatic carcinoma is likely to be even greater than suggested by our current mutational analysis.For example,we have not yet addressed the mutational status of the RBi gene,which participates in the same pathway as p16 and has been reported to be mutated in about 7% of pancreaticcarcinomas.Also,methylation abnormalities that might abrogate the expression of the p16 protein have yet to be evaluated in our collection of pancreatic carcinomas.The identification of such additional genetic targets would improve the description of the genetic profile of pancreatic carcinoma and thus enhance our understanding of the tumor-suppressive pathways that are involved in the development of this tumor type.
2008年S1期 v.25 72-73页 [查看摘要][在线阅读][下载 29K] [下载次数：22 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：33 ] Hepatocellular carcinoma(HCC)is one of the leading causes of cancer-related death in the world.The carcinogenesis of HCC is multifactorial,multifunctional and multistage.Tumor suppressor gene therapy is one of the strategies,it is mainly used to make use of tumor suppressor gene groups which can inhibit the cell growth,to prevent the expression of oncogenes or to resume the function of anti-oncogenes.But so far,there is not a particular gene to be a main tumor suppressor gene in HCC.Therefore,it is necessary to study on the new anti-oncogenes to explain pathogenesis of liver cancer and seek for the newly effective target to carry on liver cancer gene therapy.PTEN(phosphatase and tensin homolog deleted on chromosome ten)was discovered as a tumor suppressor gene.It functions as a protein tyrosine phosphatase and as a lipid phosphatase.As a lipid phosphatase,PTEN antagonizes PI3K/Akt signaling by dephosphorylating the D3 position of the inositol ring of phosphatidylinositol 3,4,5-trisphosphate(PIP3),to generate phosphatidylinositol-4,5,-biphosphate(PIP2).On the other hand,as a protein tyrosine phosphatase,PTEN can dephosphorylate itself,focal adhesion kinase(FAK)and the platelet derived growth factor receptor,involves in the migration,adhension of cells.Many researches have been testified that there is a higher frequency of negative expression of PTEN protein in hepatocellular carcinoma,the negative correlation between expression of PTEN gene and differential grade,clinic stage of HCC indicated that in activation of PTEN gene maybe a late incidence in the development of hepatocellular carcinoma and may play an important role in the genesis and development of some hepatocellular carcinoma.KLF6,a member of Krupple-like gene family,a ubiquitously expressed zinc finger transcription factor,has an important role in regulating cell growth and differentiation.Several experiments have been proved that the genetic events of tumor suppressor gene mutation and loss of allele of KLF6 gene were presented frequently in HCC.These results indicate that KLF6 may be a candidate tumor suppressor gene of HCC and plays a role during the hepatocarcinogenesis and progression of HCC.P16 gene is also called multiple tumor suppressor l(MTS1).It is the specific inhibitor of CDK4(cyclin dependent kinase 4,CDK 4).It can induce cell cycle arrest in G1 to S phase by inhibiting CDK4.The p16 gene acts in the HCC development and deletion,mutation or methylation of p16 gene are usually found in HCC.In a word,the wild-type p16 may play an important role in tumor suppression and initiate cell senescence beginning by the mechanism of inducing cell telomeric shortening and growth arrest.
2008年S1期 v.25 73-74页 [查看摘要][在线阅读][下载 29K] [下载次数：49 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：73 ] -
Objective To investigate the apoptosis effect of Total alkaloids on human gastric cancer cells SGC-7901 from Capparis spinosa(C.S)and possible mechanism of it.Methods SGC-7901 cells were treated with different concentrations of the Total alkaloids in CS.MTT assay and SRB assay were used to observe the inhibitory rate of the Total alkaloids,and fluorescence microscope,flow cytometry and used to observe the influence of the Total alkaloids on cell apoptosis and cell cycle changes of SGC-7901.Results The results showed total alkaloids can inhibit the growth of human gastric adenoma cells SGC-7901.Measurements using mononuclear cell direct cytotoxicity assay(the MTT method)shows that its cytotoxic effect on SGC-7901 is strong,with IC50 being 142.895 μg·mL-1,respectively.Results from SRB assay show that the anticancer effect of Total alkaloids is cytostatic at low concentration,with LC50 for this cells being 41.271 μg·mL-1,respectively,but it becomes mainly cytotoxic at high concentration,with GI50 for SGC-7901 being 244·932 μg·mL-1,respectively.Total alkaloids can induce apoptosis in tumor cells.Forty-eight hours after they are treated with total alkaloids of different concentrations,SGC-7901 cells are stained with Hoechst33258 fluorochromes.Observation using a fluorescence microscope reveals that total alkaloids can cause the chromatin in tumor cell nuclei to condense and fragment.The nuclei condense into a uniform,dense mass and then break up.Sprouts keep on forming on the cell membrane and then dropping off,so that the cell breaks up into several apoptotic bodies of different sizes.As total alkaloids concentration is increased,these morphological changes under the microscope become more and more clear,indicating that the proportion of cells undergoing apoptosis is gradually increasing.After treating with 75,150 and 300 μg·mL-1 of the total alkaloids in C.S for 72 h,the apoptotic rates of SGC-7901 cells were 8.7%,14.309%,0.819%.Conclusions Inducing apoptosis is one of the anti-cancer mechanism of total alkaloids of C.S.
2008年S1期 v.25 74-75页 [查看摘要][在线阅读][下载 28K] [下载次数：40 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：52 ] Objective To discuss on mechanism of the killing and apoptosis inducing effect induced by total alkaloid in the CSS(Capparis spinosa L.saponin,CSS)on human hepatocarcinoma cell Line HepG-2.Methods The killing effect of the CSS on human hepatocarcinoma cell Line HepG-2 was observed by MTT method.Morphological observation of the HepG-2 cells was completed by fluorescence microscope.This test was signed to observe the changes of the cell cycle of HepG-2 cells affected by the CSS by PI single-staining,and to observe if there were typical apoptosis peaks.The apoptosis inducing effect and changing of mitochondria membrane potential of the CSS on the HepG-2 cells were studied by flow cytometry.The effect of intracellular Ca2+ level of CSS on the HepG-2 cells was measured by laser confocal microscope.Results CSS has growth inhibiting on the HepG-2 and seems to be enhanced with the increasing concentration of CSS,and its IC50 value was 46.16 μg·mL-1.The HepG-2 cells are characteristic apoptosis morphologic changed,and the apoptosis percentage is increased to 66.652% in the 50 μg·mL-1 dosage group.The cells cycle has been changed obviously that the progresses of cells cycle of G1 period and G2 period in high dosage group have been blocked,and the cellular proportion in G2 period is decreased by the function of CSS for 24 h.The mitochondria membrane potential of HepG-2 cells induced by CSS is decreased in various degrees.In addition,the intracellular Ca2+ level is increased by the function of CSS in the middle and high dose groups.Conclusions The CSS has obviously killing and apoptosis inducing effect on human hepatocarcinoma cell Line HepG-2 by the mechanism of decreasing the mitochondria membrane potential and increasing the intracellular Ca2+ level.
2008年S1期 v.25 75页 [查看摘要][在线阅读][下载 13K] [下载次数：30 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：47 ] -
Objective To study on the mechanism of killing and apoptosis inducing effect of total alkaloid in the CSA(Capparis spinosa L.alkaloid,CSA)on human hepatocarcinoma cell Line HepG-2.Methods The killing effect of the CSA on human hepatocarcinoma cell Line HepG-2 was measured by MTT method.Morphological observation of the HepG-2 cells was completed by fluorescence microscope.The apoptosis inducing effect and changing of mitochondria membrane potential of the CSA on the HepG-2 cells were measured by flow cytometry.In addition,effect of intracellular Ca2+ level of the CSA on the HepG-2 cells was studied by laser confocal microscope.Results The CSA has obvious cytotoxicity on the HepG-2 and seems to be dose-dependent,and its IC50 value is 162.4 μg·mL-1.The HepG-2 cells have characteristic morphologic changes of apoptosis by the function of CSA,and the apoptosis percentage is higher than the natural one.The progress of cells cycle from S phase to G2 phase has been blocked,and the mitochondria membrane potential is markedly decreased,and the intracellular Ca2+ level is increased by the function of CSA.Conclusions The CSA has obviously killing and apoptosis inducing effect on human hepatocarcinoma cell Line HepG-2 by the mechanism of decreasing the mitochondria membrane potential and increasing the intracellular Ca2+ level.
2008年S1期 v.25 76页 [查看摘要][在线阅读][下载 11K] [下载次数：19 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：32 ] Objective Curcuma wenyujin,named Ezhu in Chinese,a traditional Chinese medicine,which has been shown to possess anticarcinogenic activity and used for the treatment of tumor in China,for example,hepatic cancer and leukemia.β-elemene,a component of Curcuma wenyujin,was largely reported as a main active component for anti-tumor effect of Curcuma wenyujin.However,furanodiene,another main component of Curcuma wenyujin,was seldom investigated for its anti-tumor activities.In the present study,we aim to investigate the effect of furanodiene on human leukemia HL60 cells and to study the accurate molecular mechanisms of its action.Methods Trypan blue exclusion experiment was used for cell growth inhibition assay.The apoptotic characterizations were assessed by flow cytometry analysis,AO/EB staining assay and agarose gel electrophoresis assay.The expression of apoptosis-related proteins and the release of cytochrome c from mitochondrial were detected by western blotting,and the mRNA levels of TNF-α and TNFR1 were probed by RT-PCR.Formation of TNFR1 complex was analyzed by using immunoprecipitation of TNFR1 with TRRF1/2 and RIP.Results Furanodiene(10-100 μM)treatment inhibited the growth of HL60 cells in a concentration-dependent manner.The effect of furanodiene on HL60 cells was associated with the induction of apoptosis,which was characterized by DNA fragmentation,cleavage of poly(ADP-ribose)polymerase(PARP),caspase-3,caspase-8 and caspase-9.In the Bcl-2 family proteins,Bid protein(a substrate of caspase-8)was activated by furanodiene,but Bcl-2,Bax and Bcl-xL proteins were not inuenced by furanodiene stimulation.Furanodiene elicited cytochrome c release from mitochondria into the cytosol.Moreover,furanodiene treatment caused the upregulation of TNFR1,the formation of TNFR1 complex and an obvious production of TNF-α in HL60 cells.The soluble TNFR1 receptor effectively inhibited furanodiene-induced apoptosis.Conclusions Furanodiene inhibited the growth of HL60 leukemia cells via induction of apoptosis.Furanodiene-induced apoptosis in HL60 cells is mediated by upregulation of TNF receptor 1 as well as induction of TNF-α production to activate TNFR1 signaling pathway.Our research provides insight into the molecular mechanisms on furanodiene-induced cell death,and may aid to the development of furanodiene as a new anti-tumor agent.
2008年S1期 v.25 76-77页 [查看摘要][在线阅读][下载 25K] [下载次数：42 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：50 ] -
Objective Cucurbitacins are the highly oxygenated tetracyclic triterpenes,which are predominantly found in the Cucurbitaceae family but are also present in several other families of the plant kingdom.A number of compounds of this group have been investigated for their cytotoxic,hepatoprotective,anti-inflammatory,cardiovascular and anti-diabetic activities.In China,the cucurbitacin preparation,which contains mostly cucurbitacin B and cucurbitacin E,has been clinically used for the treatment of the primary liver carcinoma.It has been previously reported that cucurbitacin E could produce cytotoxicity against a variety of cancer cells,and various mechanisms were implicated in its cytotoxic effect.The present study is to investigate the effect of cucurbitacin E on hepatoma cells in vitro and in vivo and to study their potential mechanisms of action.Methods The MTT assay was used to assess the viability of human HepG2 and BEL7402 hepatoma cells in vitro after treatment with different concentrations of cucurbitacin E.The cell cycle distribution was determined by flowcytometric analysis after propidium iodide(PI)staining.The cell cycle-related proteins were detected using western blotting analysis.Implanted mouse hepatoma H22 model was built to evaluate the growth inhibitory effect of cucurbitacin E in vivo in mice.Results Our studies found that cucurbitacin E(10-300 nM)produced anti-proliferative effect on human HepG2 and BEL7402 hepatoma cells in vitro without cytotoxicity.According to flowcytometric analysis,cucurbitacin E arrested the cell cycle at G2/M phase in both HepG2 and BEL7402 hepatoma cells after 24 h treatment.Cucurbitacin E induced the decrease in the level of CDK1 protein and the increase in the level of p21 protein,but had no effect on the levels of cyclin A,cyclin B1 and Cdc25C protein.In in vivo anti-tumor experiment,cucurbitacin E had significant inhibitory effects on the growth of mouse H22 hepatoma cells.Conclusions Cucurbitacin E inhibited the proliferation of hepatoma cells in vitro and in vivo,at least in part,through induction of cell cycle arrest at G2/M phase,which was mediated by concomitant upregulation of p21 and downregulation of CDK1.We consider that cucurbitacin E may be useful in the treatment of liver cancer.
2008年S1期 v.25 77-78页 [查看摘要][在线阅读][下载 27K] [下载次数：49 ] |[网刊下载次数：0 ] |[引用频次：1 ] |[阅读次数：58 ] Objective Flavans are a set of naturally occurring flavonoids possessing a 2-phenylchroman nucleus,which are widely distributed in the plant kingdom.A number of flavan compounds exhibit antitumor activities.In our previous report,a straightforward synthetic procedure for 2(±)-7,8,3',4',5'-pentamethoxyflavan(PMF)was developed.To be more important,PMF showed growth inhibitory effect on various human tumor cell lines,especially against HL60 cells.In the present study,we aim to investigate the molecular mechanisms of action of PMF in HL60 cells.This is the first report of the molecular mechanisms on anti-tumor effect of flavan compounds.Methods Trypan blue exclusion experiment was used for cell growth inhibition assay.Cell apoptosis,cell cycle distribution and the mitochondrial membrane potential(MMP)were assessed by flowcytometric analysis after AO/EB,PI and Rh123 flurescence staining,respectively.Cell cycle-and apoptosis-related proteins were detected using western blotting analysis.Results PMF(1-30 μM)inhibited the growth of HL60 cells in a time-and concentration-dependent manner.Antiproliferative effect of PMF on HL60 cells was associated with G2/M cell cycle arrest,which was mediated by regulating the expression of p21,Cdc25C and cyclin A proteins and inhibiting the phosphorylation of Cdc2 at Thr161.The prolonged PMF treatment also induced apoptosis of HL60 cells,which was characterized by DNA fragmentation,cleavage of poly(ADP-ribose)polymerase,caspase-3,caspase-8 and caspase-9,changes of Bcl-2 and Bax expression and a decrease in the mitochondrial membrane potential(MMP).Furthermore,caspase-3 inhibitor,not caspase-8 inhibitor and caspase-9 inhibitor,completely blocked PMF-caused apoptosis.Conclusions PMF inhibited the growth of HL60 cells via induction of G2/M arrest and apoptosis.Blockade of cell cycle was associated with the downregulation of Cdc2 complex activity.Both death receptor and mitochondrial apoptotic pathways explained PMF-caused apoptosis.
2008年S1期 v.25 78-79页 [查看摘要][在线阅读][下载 23K] [下载次数：29 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：43 ] -
Objective Cefditoren,a third-generation cephalosporin antibiotics,has been used in clinic extensively.Whether Mrp2 or other canalicular transporters such as Bcrp and P-gp are involved in the biliary excretion of cefditoren is unknown.This study is performed to investigate the role of the canalicular transporters in the biliary excretion of cefditoren and the effect of cefditoren on expression levels of some hepatic transporters.Methods We examined the hepatobiliary disposition of cefditoren using probenecid,novobiocin and verapamil as the inhibitors of Mrp2,Bcrp and P-gp respectively in perfused rat livers.The concentration of cefditoren in the perfusate and bile were determined by RP-HPLC with ultraviolet detection at 295nm using a mobile phase composed of 0.1% ammonium acetate-methanol(65∶35).We also investigated the effects of cefditoren on expression of hepatic transporters.The change in mRNA of main canalicular transporters was investigated by RT-PCR and Western blot after administration of cefditoren.Results The values for the hepatic extraction ratio did not change,whereas cumulative biliary excretion rates of cefditoren were significantly reduced to 43.78% and 79.52% over 25 min in the perfused probenecid and novobiocin rats,respectively.After oral administration of cefditoren,the expression levels of Mrp2,Bcrp,Oat2 mRNA were markedly up-regulated,while Mdr1a and Oct1 mRNA were down-regulated by RT-PCR.In concordance with RT-PCR results,Mrp2 expression level was up-regulated by Western blot.Conclusions Mrp2 and Bcrp mediated the biliary excretion of cefditoren,whereas P-gp had no contribution to the transportation of cefditoren into bile.The expression levels of Mrp2,Bcrp and Oat2 mRNA were up-regulated and the expression levels of Mdr1a and Oct1 mRNA were down-regulated by cefditoren.These results provide important data for drug-drug interaction.
2008年S1期 v.25 79-80页 [查看摘要][在线阅读][下载 20K] [下载次数：67 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：53 ] Objective To evaluate the inhibitory effect of tectorigenin on the proliferation of human hepatoma cells SMMC-7721.Methods Tectorigenin was added into SMMC-7721 human hepatoma cells in log phase.After 24 hours the morphologic change was observed with an inverted microscope.The inhibitory effect on the proliferation of tumor cells was evaluated by MTT.The early and late apoptosis rate were measured by flow cytometry using Annexin V-FITC /PI double staining and PI single staining respectively.Results After cultivated with tectorigenin for 24 hours,the hepatoma cells became smaller,rounder and thicker.The adherent cells in experimental group were much fewer.The results of MTT showed that tectorigenin could inhibit the cell proliferation in a concentration-dependence manner from 1.00 μg·mL-1 to 8.00 μg·mL-1.48-hour maximal inhibition rate could reach 76.57%,IC50 was(3.71±1.17)μg·mL-1(n=5).The 6-hour early apoptosis rate of hepatoma cells was(28.05±1.72)%,(56.17±2.14)% and(88.54±3.04)% respectively after cultivated with 5.00,10.00 and 20.00 μg·mL-1 tectorigenin.There were significant difference between the experimental groups and control group whose early apoptosis rate was(6.77±0.81)%(P<0.01).The 48-hour late apoptosis rate was(9.33±0.85)%,(17.02±1.38)% and(38.04±2.03)% respectively,there were also significant difference between the experimental groups and control group(P<0.05).Conclusions Tectorigenin has significant inhibitory effect on the proliferation of SMMC-7721 human hepatoma cells within the range of 1.00 to 16.00 μg·mL-1 and the mechansim may be related to promoting apoptosis.
2008年S1期 v.25 79页 [查看摘要][在线阅读][下载 10K] [下载次数：47 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：70 ] - 李娜;任婕;唐宏涛;魏敏杰;
目的研究HFI对卵巢癌裸鼠移植瘤的生长抑制作用。方法建立人卵巢癌裸鼠皮下移植瘤模型,当瘤体积增长到100～200mm3时,随机分成4组(n=10),然后分别给予不同浓度(0.5mg·kg-1,0.25mg·kg-1)的HFI,裸鼠移植瘤体积及裸鼠体重每隔一天监测一次。结果各组的裸鼠体重没有显著性差异(P>0.05)。HFI(0.5mg·kg-1)剂量组和(mg.kg-1)剂量组的肿瘤体积增长速度显著低于阴性对照组(P<0.05)。移植瘤体积及瘤体重量在HFI(0.5mg·kg-1)剂量组和(0.25mg·kg-1)剂量组分别为[(911±286.631)mm3,(0.495±0.115)g]和[(1291.545±827.216)mm3,(0.542±0.237)g]显著低于阴性对照组[(1410.965±341.340)mm3,(0.714±0.124)g(P<0.05)]。HFI(0.5mg·kg-1)剂量组和(0.25mg·kg-1)剂量组的移植瘤瘤体抑瘤率分别为40.04%,16.07%,显著高于阴性对照组(0%)。HFI(0.5mg·kg-1)剂量组的裸鼠移植瘤体积与裸鼠体重之比的增长速度明显低于阴性对照组(P<0.05)。结论HFI能够显著抑制裸鼠移植瘤的生长。
2008年S1期 v.25 80页 [查看摘要][在线阅读][下载 10K] [下载次数：65 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：123 ] - 赵琳;王麟;金锋;马文峰;任婕;温晓燕;何苗;魏敏杰;
目的探讨中国散发性乳腺癌中ERα蛋白表达和ERα基因启动子甲基化的相关性。方法通过甲基化特异性PCR法检测138例乳腺癌肿瘤组织中ERα基因启动子区四个CpG岛密集区域甲基化情况,免疫组织化学方法检测ERα,PgR蛋白表达。结果138例肿瘤组织中有83例发生ERα基因启动子甲基化(60.1%),69例ERα阴性标本有57例发生甲基化(82.6%)。ERα蛋白失表达与ERα基因启动子甲基化具有相关性。此外,ERα基因启动子甲基化与PgR蛋白低表达相关。(76%vs24.1%;P<0.00001)。结论中国散发性乳腺癌普遍存在ERα基因启动子甲基化,ERα基因启动子甲基化与ERα、PgR蛋白低表达相关,ERα基因的表遗传学改变在中国散发性乳腺癌发生发展中具有重要作用。
2008年S1期 v.25 81页 [查看摘要][在线阅读][下载 10K] [下载次数：135 ] |[网刊下载次数：0 ] |[引用频次：1 ] |[阅读次数：91 ] -
Objective To comparatively study anti-free radical and cytoprotective effects of quercetin(Q)and its monoglucoside isoquercetin(I),diglucoside rutin(R),which differs only in glycosyl-substitution at C-3 position of the molecules,using anoxia/hypoglycemia-induced cell injury model and thereby to explore the structure-effect relationship thereto.Methods The cell injury model was established by HEK293 cells cultured in vitro with Na2S2O3 plus sugar-free Earle's fluid as incubation medium;Cell survival rate(CSR),total antioxidant capacity(TAC),SOD and LDH levels were determined;The effect intensity of the 3 flavonoids were compared by means of IC50,the concentration required to achieve 50% inhibition of the changes in the above indices in injured cells.Results Q,I and R all concentration-dependently elevated CSR,TAC and SOD,and reduced LDH level;the all of IC50s for the above indices were ranked in order of IC50,Q<IC50,I<IC50,R,namely,the effect intensity should be Q>I>R.Conclusions The 3 structurally similar flavoloids all have significant and concentration-dependent anti-free radical and cyto-protective effects with the intensity being in order of aglycone>monoglucoside>diglucoside;the substitution of-OH by sugar group at C-3 position of flavoloids and increase in the sugar-substituent number are associated with the effect intensity reduced;namely,the intensity of these effects of flavonoids is negatively related the substutution by sugar group at C-3 position.
2008年S1期 v.25 81-82页 [查看摘要][在线阅读][下载 19K] [下载次数：19 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：58 ] Objective To make a review about MAPK and apoptosis of tumor cells.Methods We collected a large number of related experimental papers,and summarized key points.Results mitogen activated protein kinase(MAPK)is one of the four biggest signal transduction systems which contain four subtribes named p38,ERK5,ERK and JNK/SAPK respectively.MAPK pathways constitute numerous modular network that regulates a variety of physiological processes,such as cell growth,roliferation,differentiation,and apoptotic cell death.Specially,the function of induced apoptosis in tumor cells has gradually become main focus.Both in-vitro and ex-vivo findings demonstrated that in apoptotic tumor cells the level of phosphorylation of JNK kinase is significantly improved.That means JNK kinase is activated in these tumor cells.At the same time,contrary to JNK kinase,the activity of ERK kinase is usually weakened.So,for most apoptotic tumor cells,JNK is a positive factor,however,ERK kinases is a negative factor.As for the p38 kinase,which can be activated to outside stimulus,also has the promotion of apoptosis.Importantly,ERK kinase activity is suppressed by JNK/p38 kinase during apoptosis induction.Further study demonstrate that the regulatory mechanisms of MAPK in apoptotic tumor cells are:working on upstream of caspase;starting death receptor channel;activating pro-apoptotic Bcl-2 protein family;changing mitochondrial permeability;participating in Fas/Fasl-mediated apoptosis;enhancing the expression of TNF-a and so on.Conclusions The relationship between MAPK and apoptosis of tumor cells is intimate.It is expected to be a new target for tumor in clinical treatment.
2008年S1期 v.25 82页 [查看摘要][在线阅读][下载 9K] [下载次数：41 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：38 ] -
Objective To search the effect of Chinese traditional medicine "Shang Lu Yu Wang Gao"(SLYWG)on the ascites induced by tumor,and its mechanism.Methods The tumor ascites model and diuretic experiments were introduced to evaluate the effect of SLYWG.Physical characteristics,the tumor cell counting,volume of the ascites,protein content in ascites,the characters of ascites,the life duration of S180 tumor bearing animals as the indexes of evaluation.the diurtic experiments were performed on rats nad rabbits,the osmotic pressure,K+,Na+,Cl-,Ca2+ and pH in urine were determined.Results The inhibitions to ascites of SLYWG were displayed in three dosage(30 g·kg-1,15 g·kg-1 and 7.5 g·kg-1).Ascites caused by tumor was significantly inhibited by the local administration of SLYWG.The increase of mice ascites was slow down,the content of ALB and the TP in ascites were decreased,the surviving time of mice was extended.SLYWG had remarkable diuresis effect on the rats and rabbits,it could reduce the osmotic pressure of urine,decrease the exclude of K+ but had no effect on the Na+,Cl-,Ca2+ and pH in urine.Conclusions Tumor ascites was significantly inhibited by the ventral administration of SLYWG.SLYWG had diuretic effect in rats and rabbits,it reduced the osmotic pressure of urine,decrease the exclude of K+ but had no effect on Na+,Cl-,Ca2+ and pH of urine.
2008年S1期 v.25 83-84页 [查看摘要][在线阅读][下载 24K] [下载次数：14 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：41 ] Objective To investigate the anticancer effect of xanthoceraside in vitro and the possible mechanisms involved in the potent antiproliferative effect on human breast cancer MCF-7 cell.Methods The inhibition rate of different tumor cells and human peripheral blood lymphocyte cells was investigated by MTT assay.AO/EB double fluorescent dye staining was used to investigate the morphology changes of MCF-7.The DNA agarose gel electrophoresis was further used to observe the DNA Fragmentation.Flow cytometry was employed to investigate the volume changes,the cell cycle distribution and the mitochondrial membrane potential of MCF-7.The antioxidant N-acetylcysteine(NAC)was chosen to detect the influence on oxidant-stress system of MCF-7 cells.Necrostatin-1 was next chosen to detect the influence on antiproliferative effect of xanthoceraside-treated MCF-7 cells.Results Xanthoceraside could inhibit the proliferation of tumor cells significantly in a dose-dependent manner and it has no cytotoxic effects on human peripheral blood lymphocyte cells in vitro.Cytoplasm vacuole was observed but no significant condense of nuclear chromatin was found,meanwhile,MCF-7 cells were bigger and smear was observed by agarose gel electrophoresis after MCF-7 cells were exposed to xanthoceraside.The cell cycle distribution of MCF-7 was greatly changed after exposure to xanthoceraside with an obvious G1 arrest.The mitochondrial membrane potential showed significant decrease.NAC attenuate the antiproliferative effect of xanthoceraside-treated MCF-7 cells but necrostatin-1 had no effects.Conclusions Xanthoceraside-induced necrosis might be dependent of mitochondria,meanwhile reactive oxygen species(ROS)participated in it.The xanthoceraside-induced MCF-7 cell death might not be the cell necrosis which initiated by Fas/TNFR and must be through RIP1 kinase.
2008年S1期 v.25 83页 [查看摘要][在线阅读][下载 11K] [下载次数：67 ] |[网刊下载次数：0 ] |[引用频次：3 ] |[阅读次数：72 ] -
Objective This paper was aimed to investigate the time-dependence of toxicity and pharmacodynamic action in Cyclophosphamide-Cisplatin-Adriamycin(CAP)combined chemotherapy and to find theoptimal administrating time to provide the better dosage regimen for the clinical cancer treatment.Methods S180 tumor bearing mice were firstly divided into six groups,and then were injected(ip.)with CTX(20 mg·kg-1),DDP(1 mg·kg-1),ADM(1 mg·kg-1)at different time(10:00 h,14:00 h,18:00 h,22:00 h,02:00 h and 06:00 h),respectively.In all groups ADM(1 mg·kg-1)were administed every three days.Finally the various related data was collected to assess the time-dependence of toxicity and pharmacodynamic action in CAP combined chemotherapy.Results The tumors could be inhibited by CAP combined chemotherapy in all the tested groups at different time,the group administed at 02:00 h showed the best action.The results of tumor cell cycle analysis showed that DNA synthesis decreased after the chemotherapy,most significantly at 22:00 h.The levels of tumor cell apoptosis-related proteins p53 and Bcl-2 increased after combination chemotherapy,whereas the level of Bax declined.And p53 changed most remarkably from 18:00 to 22:00 h,and for Bcl-2 and Bax that was from 02:00 to 10:00 h.The distribution of bone marrow cells cycle appeared sub-G1 peak,which is the phenomenon of apoptosis,at 02:00 h and 10:00 h was the most significant.At the same time the proportion of G1 and S-phase decreced,which indicates DNA synthesis of bone marrow cell declined.A time-dependent 19 KD activated fragments of Caspase-3 appeared by western blotting determination,at 02:00 h and 10:00 h.Conclusions The CAP combined chemotherapy had the best pharmacodynamic action during 22:00-02:00 h and the worst during the 10:00-14:00 h.As refer to toxicity,the most toxic time was during 06:00-14:00 h.
2008年S1期 v.25 84页 [查看摘要][在线阅读][下载 13K] [下载次数：19 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：51 ] Objective To explore the effect and mechanism of diallyl trisulfide on the activity of NADPH oxidase in Hl-60 cells.Methods HL-60 cells were treated with DATS at a indicated concentration for 0,1,3,6,12 hours,respectively.The activity of NADPH oxidase was measured by the reduction of the yellow dye nitroblue tetrazolium(NBT).The mRNA expression of NADPH oxidase subunits,including gp91phox,p47 phox,p22 phox,Rac2 and Rac1,was detected by RT-PCR.The protein expression of p67 phox,gp91 phox and Rac2 was analyzed by Western blot.The cell membrane fractions were prepared according to the instruction of Mem-PER kit from Pierce Corp.Results The results showed that reduction ability of HL-60 cells for NBT markedly increased in a concentration-dependent manner following DATS incubation for 3 and 6 hours(P<0.05).HL-60 cells treated by DATS at a concentration of 150 μM for 3 hours have a maximal reduction effect for NBT.The results from RT-PCR indicated that mRNA expression of NADPH oxidase subunits,including p47phox,gp91 phox,p22 phox,Rac2 and Rac1,significantly increased in a concentration-dependent manner in HL-60 cells treated by DATS.The results from western blot showed that HL-60 cells following DATS incubation have a higher level expression of Rac2 and gp91phox,compared with untreated-HL-60 cells.Our results also indicated that a maximal expression level of p47phox,gp91 phox,p22 phox,Rac2 and Rac1in HL-60 cells is present at 3 hours following DATS incubation.We found that levels of both Rac2 and p67phox was reduced in the cytosolic fraction and meanwhile increased in the membrane fraction following HL-60 exposed to DATS,Which is dependent on the concentration and time of DATS treatment.Furthermore,the level of both Rac2 and p67phox located to the plasma membrane translocation was maximized following 150 μM of DATS incubation for 3 hours.Conclusions DATS induce the activation of NADPH oxidase by both up-regulating the expression of NADPH oxidase subunit and translocating the cytosolic Rac2 and p67 phox subunit to the plasma membrane in HL-60 cells.
2008年S1期 v.25 85页 [查看摘要][在线阅读][下载 10K] [下载次数：51 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：90 ] -
Objective To explore the production and cytotoxicity of the reactive oxygen species(ROS)induced by diallyl trisulfid(DATS)in HL-60 cells.Methods HL-60 cells were either treated with various doses of DATS alone,or DATS combination with Apocynin,a specific NADPH oxidase inhibitor,or with antioxidant N-acetyl-L-cysteine(NAC)for 0,1,3,6,12 and 24 hours,respectively.The intracellular ROS level was measured by flow cytometry.The activity of NADPH oxidase was evaluated by NBT reduction experiment.The content of both malondialdehyde(MDA)and the protein carbonyl was analyzed by spectrophotometer.Results The results from flow cytometry indicated that DATS significantly increased the intracellular ROS level in HL-60 cells(P<0.05),which is a dose-and time-dependent.The fluorescence intensities of ROS reached at maximuam when HL-60 cells were incubated with 150 μmol·L-1 DATS for 3 hours.The NBT reduction experiment showed that DATS activated NADPH oxidase which had highest activity when cell were exposed to 150 μmol·L-1 DATS for 3 hours.Results DATS induced MDA and protein carbonyl production in HL-60 cells.Furrthermore,both MDA and protein carbonyl in the cells exposed to 150 μmol·L-1 DATS for 3 hours reached the highest level.Apocynin and NAC could attenuate the production of MDA and protein carbonyl,which suggested that ROS induced by DATS was involved in the toxicity to cells.Conclusions DATS induce ROS production through activating NADPH oxidase in HL-60 cells.ROS induced by DATS increase the oxidation of the membrane lipid and the protein of HL-60 cell.
2008年S1期 v.25 86页 [查看摘要][在线阅读][下载 10K] [下载次数：48 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：100 ] Objective To explore the effects and mechanisms of cytoplasmic M-CSF on the proliferation,migration and invasion of HeLa cells.Methods Both pCMV/cyto/myc vector and pCMV/cyto/myc-M-CSF vector was transfected into HeLa-cell by transfectaimine.After screening by G418,the positive clones were amplified and confirmed by RT-PCR,Western blot and immunocytochemistry.The effect of cytoplasmic M-CSF on the proliferation of HeLa cells were analyzed by cell conuting and antisense oligonucleotides.The migration and invasion of cell was measured by in vitro Transwell assay and Matrigel-coated polycarbonate filters.The expression of cyclinE,cyclinD1/2/3,CDK2/4/6,Rac1,and matrix metalloproteinase 2 and 9(MMP2/9)were assayed by semiquantitative RT-PCR.And expression of both α-tubulin and cdc42 were displayed by immunofluorescence.The activity of MMP2 was detected by gelatin zymography.Results Results A cell line(referred as to HeLa-M cell)that highly expresses cytoplasmic M-CSF was successfully established in the test.Our result indicated that HeLa-M cell had a larger volume,faster growth rate and shorter doubling time than either pCMV/cyto/myc transfected HeLa cells(referred as to HeLa-C cell)or untransfected HeLa cells(referred as to HeLa cell).M-CSF-specific antisense oligonucleoside significantly inhibited HeLa-M cell proliferation and had little effect on either HeLa-C cell or HeLa-C cell growth.Cytoplasmic M-CSF up-regulated both the expression of cyclinE,cyclinD1 and cyclinD3,CDK2,CDK 4 and CDK6,a Rho GTPase ralative protein(Rac1),cdc42 and MMP2,but had little effect on expression of MMP9 and cyclin D2.Furthermore,cytoplasmic M-CSF induced the rearrangement of the α-tubulin in HeLa cells and significantly promoted the migration and invasion of HeLa cells in vitro.Conclusions Cytoplasmic M-CSFs up-regulate the expression of cyclinE,cyclinD1 and cyclinD3,CDK2,CDK 4 and CDK6 and induces the proliferation of HeLa cells.Cytoplasmic M-CSFs up-regulate the expression of Rac1 and cdc42 and cause the rearrangement of the α-tubulin in HeLa cells.Furthermore Cytoplasmic M-CSFs increase both the expression and activity of MMP2 and promote the migration and invasion of HeLa cell in vitro.But cytoplasmic M-CSFs have little effect on expression of cyclin D2 and MMP9.
2008年S1期 v.25 86-87页 [查看摘要][在线阅读][下载 24K] [下载次数：38 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：66 ] -
Objective To explore the effect of the interaction between microphage colony-stimulating factor(M-CSF)and minichromosome maintenance protein-7(Mcm7)on DNA replication in HeLa cells.Methods pCMV/nuc/myc,pCMV/nuc/GFP and pCMV/nuc/M-CSF vector were stably transfected into HeLa cells by Lipofectamine,respectively.After screening with G418,the expression and localization of M-CSF in HeLa cells were verified by RT-PCR,Western blot and immunofluorescence staining.The statue and interaction between intracellular M-CSF and Mcm7 in HeLa cells was analyzed by co-immunoprecipitation.The effect of the interaction between M-CSF and Mcm7 on DNA replication was analyzed by a mammalian cell or cell-free DNA replication system in vitro.Results The results indicated that the M-CSF-transfected HeLa cells stably express both M-CSF mRNA and protein,and that M-CSF protein is located to the nuclei of HeLa cells mentioned above.To further analyze the status and interaction between intracellular M-CSF and Mcm7,the Mcm7 from HeLa cells was precipitated with anti-Mcm7 antibody and followed by Protein A/G PLUS agarose.The precipitation was blotted with anti-M-CSF monoclonal antibody.The results show that M-CSF was coprecipitated with Mcm7,so intracellular M-CSF existed in Mcm7-bound state.The DNA replication experiments reveal that a higher percentage of the replicating nuclei is present either in unsynchronized or in both synchronized G1 and S phase M-CSF-transfected HeLa cells,compared with both pCMV/nuc-transfected and un-transfected HeLa cells,which suggests that interaction between M-CSF and Mcm7 promote both the initiation and elongation of DNA replication.Conclusions M-CSF directly interacts with Mcm7.The interaction between M-CSF and Mcm7 promotes both the initiation and elongation of DNA replication.
2008年S1期 v.25 87-88页 [查看摘要][在线阅读][下载 22K] [下载次数：36 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：65 ] - 王立辉;杨静玉;申英基;吴春福;
目的研究蛋白酶体抑制剂MG132对胃癌细胞系AGS和SNU484细胞成活率和凋亡情况的影响及其可能的分子机制。方法蛋白酶体抑制剂MG132(1μM,10μM)处理胃癌细胞系AGS和SNU484。利用MTT法检测细胞生长状态,采用流式细胞仪测定细胞凋亡情况,利用Western blot法检测肿瘤抑制基因SMAD4蛋白表达水平。结果MG132能够以时间和剂量依赖的方式抑制AGS和SNU484的细胞增殖,且AGS对MG132的敏感性要高于SNU484细胞。MG132呈剂量依赖的方式诱导AGS和SNU484细胞凋亡。探讨相关分子机制发现MG132能够上调SMAD4蛋白的表达水平。结论用MG132处理胃癌细胞可引起细胞增殖抑制,其可能的分子机制为上调肿瘤抑制基因SMAD4的表达。蛋白酶体抑制剂可能会成为一类新的抗胃癌的药物。
2008年S1期 v.25 88页 [查看摘要][在线阅读][下载 8K] [下载次数：131 ] |[网刊下载次数：0 ] |[引用频次：1 ] |[阅读次数：123 ] - 杜蕾;杨静玉;张凤娇;吴春福;
目的探讨葡萄籽提取物F3(儿茶素高聚体,聚合度为10-33)对人恶性胶质瘤细胞株U87细胞增殖和趋化的影响。方法采用MTT法检测F3对U87细胞的增殖抑制作用。光镜及AO/EB染色观察细胞形态的变化。Boyden小室法探讨F3对U87的体外趋化作用。结果F3能抑制U87细胞的增殖,其作用呈明显的时间和剂量依赖性,给药24h、48h、72h的IC50分别为88μg·mL-1、53μg·mL-1、41μg·mL-1。光镜及AO/EB染色观察F3(10μg·mL-1、30μg·mL-1、60μg·mL-1、100μg·mL-1)作用24h使U87细胞形态发生明显改变。F3(1.0μg·mL-1、2.5μg·mL-1、5.0μg·mL-1、10.0μg·mL-1)预先作用1h能抑制FPR激动剂fMLF(10nM)诱导的U87细胞的趋化,显示一定的剂量依赖性关系。结论F3可抑制U87细胞的增殖,并可抑制FPR激动剂fMLF诱导的U87细胞的趋化。
2008年S1期 v.25 88-89页 [查看摘要][在线阅读][下载 15K] [下载次数：181 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：92 ] - 张雯;王立辉;陈国良;杨静玉;吴春福;
目的对姜黄素进行了相应的修饰得到了二十五个姜黄素衍生物,并在细胞水平对这些化合物的体外抗肿瘤活性及其机制进行初步探讨。方法采用MTT法研究姜黄衍生物(6.25μM、12.5μM、25μM和50μM)在体外对HL-60的成活率的影响,并采用吖啶橙(AO)/溴化乙锭(EB)荧光双染法染色及流式细胞术对其作用机制进行了初步探讨。结果MTT实验结果表明姜黄素衍生物对人白血病细胞株HL-60的存活率具有一定的影响,其中9#、12#作用最强,且具有时间和剂量依赖性。AO/EB荧光双染法染色及流式细胞术(PI)结果表明姜黄素衍生物9#、12#可以显著的诱导HL-60细胞凋亡,并呈剂量和时间依赖性。结论姜黄素衍生物9#、12#可能通过诱导细胞凋亡抑制细胞生长。
2008年S1期 v.25 89页 [查看摘要][在线阅读][下载 7K] [下载次数：155 ] |[网刊下载次数：0 ] |[引用频次：1 ] |[阅读次数：118 ] - 张凤娇;杨静玉;牟艳华;孙宝山;平轶芳;王吉民;卞修武;吴春福;
目的探讨葡萄籽提取物F2对人恶性胶质瘤细胞U-87增殖的影响及对其甲酰肽受体(FPR)功能的影响。方法采用MTT法检测F2对U-87细胞成活率的影响。光镜及AO/EB染色观察细胞形态学变化。流式细胞术考察F2对U-87细胞周期及线粒体膜电位的影响。趋化实验方法考察F2对fMLF诱导的U-87细胞趋化的影响。采用Fura-2双波长测定法考察F2对fMLF诱导的U-87细胞钙动员的影响,用westernblot方法考察F2对fMLF诱导的U-87细胞ERK1/2磷酸化的影响,并用激光共聚焦方法考察F2对U-87细胞FPR表达的影响。结果F2能显著抑制U-87细胞的增殖,其作用呈明显的时间和浓度依赖性,药物作用24h、48h、72h的IC50分别为75μg·mL-1、33.6μg·mL-1、25μg.mL-1。光镜及AO/EB观察F2作用48h能使U-87细胞形态发生明显改变,包括细胞变圆,胞浆内出现许多大大小小的空泡。F2能显著降低U-87细胞线粒体膜电位,诱导U-87细胞G2/M期阻滞并能诱导有典型paraptosis形态特征的细胞死亡。非细胞毒浓度的F2还能显著抑制FPR激动剂fMLF(10nM)诱导的U-87细胞趋化,且能显著抑制fMLF诱导的U-87细胞钙动员及ERK1/2磷酸化。而且F2还能显著降低在胶质瘤的增殖、迁移及血管生成中起重要作用的FPR的表达。结论F2不仅能显著抑制U-87细胞的增殖,还能通过抑制FPR激动剂fMLF诱导的U-87细胞的趋化而抑制肿瘤细胞迁移,能抑制其FPR的表达,是一种很有开发潜力的新型抗胶质瘤药物。
2008年S1期 v.25 89页 [查看摘要][在线阅读][下载 7K] [下载次数：218 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：198 ] Objective To test the hypothesis that increased plasma levels of Lp(a)may enhance the development of atherosclerosis in the setting of hypercholesterolemia.Methods The plasma Lp(a)was analyzed by SDS-PAGE Western blotting and quantitated using specific ELISA kits.Plasma total cholesterol,triglycerides and HDL-cholesterol were determined using Wako assay kits.The left coronary artery was used for the evaluation of coronary atherosclerosis(stenosis %).For quantitative study of the lesions in coronary atherosclerosis,hematoxylin-eosin and Elastica-van Gieson staining were used.To study cellular components(SMC vs.macrophages)and Lp(a)deposits in the lesions,immunohistochemical staining was performed and then image analysis system was used.Results Plasma total cholesterol,triglycerides,or HDL-C were not significantly different between transgenic(Trg)and nontransgenic(nonTrg)rabbits.Trg rabbits had 200% increase in coronary stenosis caused by atherosclerosis.The lesions of Trg WHHL rabbits contained more SMCs and less macrophage than those of nonTrg WHHL rabbits.Conclusions The results suggest that increased plasma levels of Lp(a)enhance the development of coronary atherosclerosis.
2008年S1期 v.25 90-91页 [查看摘要][在线阅读][下载 20K] [下载次数：24 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：69 ] -
Objective To determine the antiplatelet and antithrombotic efficacies of MV1 serine protease on coronary arterial thrombosis in a canine model of unstable angina.Methods Pentobarbital-anesthetized Beagles(total of 30)were used in which acute damage of the proximal left circumflex coronary artery,together with mechanical stenosis,produced the phenomenon of cyclic flow reduction(CFR)in the Folts model of unstable angina.When the platelet plug was removed by rubbing the vessel,the occlusion returned reproducibly for at least 3 hours in control studies.To evaluate the antithrombotic efficacy of MV1,CFR was first established over a period of one hour,thereafter,MV1(0.3,0.6 mg·kg-1 i.v.bolus),Batroxobin(0.3 BU·kg-1 i.v.bolus),Tirofiban(40 μg·kg-1,i.v.bolus),or vehicle was administered and observations continued for two additional hours.Platelet aggregation induced by adenosine diphosphate(ADP),arachidonic acid(AA),collagen(CG)was measured by the method of born,and thrombin time(TT),prothrombin time(PT),activated partial thromboplastin time(APTT)and fibrinogen(Fbg)were measured using coagulation methods,bleeding time was measured according to previous described methods.Results MV1 dramatically inhibited the frequency of CFR dose-dependently and the frequency of CFR decreased by 65%,80% respectively at 1 h than that in control group's after MV1 0.3,0.6 mg·kg-1 administration,further more the frequency decreased by 75%,90% respectively at 2 h.MV1 eliminated thrombus formation in 5 of 6 dogs at 0.6 mg·kg-1,and the time for CFR absolute disappearances of MV1 at a dose of 0.6 mg·kg-1 was shortened to 5±2 min(the time was more than 120 min in all dogs of control group).Platelet aggregation induced by ADP,AA,CG was inhibited effectively by MV1 0.3,0.6 mg·kg-1 TT,PT prolonged gently after MV1 administration,and MV1 produced an approximate 40% degradation of Fbg,but MV1 did not have any effects on APTT.There was a tendency for prolonged bleeding time with MV1 administration.Conclusions These studies showed that as a novel serine protease,MV1 provides favorable antithrombotic activity in vivo with inhibition of platelet aggregation and fibrinogenolytic activity.The results indicated that MV1 has reliable therapeutical efficacy on unstable angina pectoris.
2008年S1期 v.25 90页 [查看摘要][在线阅读][下载 11K] [下载次数：21 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：38 ] - 王崴;金万宝;魏敏杰;
目的探讨糖尿病大鼠心肌病变是否与钠钙交换蛋白Ⅰ亚型(NCX1)及肌浆网钙泵2a亚型(SERCA2a)表达水平变化有关。方法大鼠腹腔注射链佐霉素制备实验性糖尿病大鼠模型。将大鼠成模后分别于4w、6w和8w时取心肌组织,进行病理学检查及计算心脏相对重量观察心肌病变程度;应用RT-PCR方法扩增NCX1和SERCA2a两种产物,计算NCX1与SERCA2amRNA相对数量的变化,并与相应周数的正常对照组进行比较。结果糖尿病各组心脏湿重与体重的比值均明显高于对照组,病理检查显示心肌细胞呈不同程度变性坏死;4w,6w糖尿病组NCX1和SERCA2amRNA的量有所降低,但无统计学差别,而8w时,糖尿病组NCX1和SERCA2amRNA相对含量比对照组明显减少(P<0.05)。结论在糖尿病合并心肌病变时,大鼠心肌的NCX1与SERCA2a的mRNA水平降低,提示其心脏功能的减退与NCX1和SER-CA2a的mRNA水平降低有一定关系。
2008年S1期 v.25 91页 [查看摘要][在线阅读][下载 9K] [下载次数：116 ] |[网刊下载次数：0 ] |[引用频次：1 ] |[阅读次数：92 ] -
Objective To examine the effects of Veratrum nigrum L.Var.ussurience Nakai alkaloids(VnA)on angiotensin Ⅱ(AngⅡ)-induced cardiomyocyte hypertrophy and to explore its possible mechanism.Methods The cadiocytes were induced by AngⅡ to set up myocardial hypertrophy model,the animals were divided into six groups according to the different treatments:control group,model group,positive control group,VnA group(low,middle and high dose).The cell protein content,the cell diameter and the expression of calcineurin(CaN)were measured respectively by BCA method,the micrometer and immunofluorescence analysis.Results VnA(middle and high dose)and Captopril inhibited significantly the increase in the protein content induced by AngⅡ(P<0.01).VnA and Captopril inhibited significantly the increase in the diameters induced by AngⅡ(P<0.01).By immunofluorescence analysis,the expression of calcineurin(CaN)was obviously increased in the AngⅡ-induced model group.VnA decreased the expression of CaN significantly.Conclusions VnA could inhibit the cardiomyocyte hypertrophy induced by AngⅡ significantly in a dose-dependent manner.The possible mechanism may be related to the inhibition of CaN expression.
2008年S1期 v.25 91-92页 [查看摘要][在线阅读][下载 23K] [下载次数：40 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：82 ] Objective To investigate the effect and mechanism of Celastrus Orbiculatus total terpenoids on lipid metabolism in hyperlipidemia mice.Methods ICR mice were selected as investigated subject.The hyperlipemia mice models were made with feeding high-fat forage and were randomly divided into six groups:the normal group,the model group,the positive control group(treated with simvastatin)and the three groups treated with Celastrus Orbiculatus total terpenoids with low,medium and high dosage,respectively.Each group included eight mice.The control group was fed normal forage,but other groups were fed high fat forage.All groups were allowed to drink water freely.Since the first day when the models were made,intragastric administration had been adopted.The normal group was fed normal forage without intragastric administration;the model group was received physiological saline 20 mL·kg-1·d-1 with intragastric administration;the positive control group received simvastatin 2.6 mg·kg-1·d-1 with intragastric administration;the three treated groups received Celastrus Orbiculatus total terpenoids 60 mg·kg-1·d-1,120 mg·kg-1·d-1,200 mg·kg-1·d-1 with intragastric administration respectively.Each group was weighed once a week.On the basis of establishing hyperlipidemia mice model,blood lipids,lipid metabolic enzyme,antioxidative capacity were investigated after 21 days feeding of high-fat forage.Results Compared with model group,TC and TG in mice treated with Celastrus Orbiculatus total terpenoids all reduced and HDL-C raised obviously(P<0.01).Celastrus orbiculatus total terpenoids was shown to decreased MDA content in both serum and liver,increased serum SOD activity and inhibited the activity of the cholesteryl ester transfer protein(CETP).Conclusions Celastrus Orbiculatus total terpenoids could remarkably modulate the lipid metabolic disorder in hyperlipidemia mice,and has a certain regulating function on lipoprotein,inferring that it could reduce the occur of atherosclerosis.The mechanism of regulating lipid metabolism might be related with decreasing the activity of CETP and increasing antioxidative capacity.
2008年S1期 v.25 92页 [查看摘要][在线阅读][下载 14K] [下载次数：37 ] |[网刊下载次数：0 ] |[引用频次：1 ] |[阅读次数：59 ] -
Objective To explore the influence of styptic fiber on clotting time in rabbits so as to provide experiment data for its development.Methods Onto 0.1 mL aliquots of citrated anti-coagulant rabbit blood placed in a surfacial plate 25 ul of 0.2 mol·L-1 CaCl2 solution was dropped,and mixed well with glass stirrer;the resulting mixture was immediately capped with a piece of styptic fiber(test product group)or absorptive gelatin sponge(positive control group)of 2 cm diameter.Then,the surficial plate was rinsed with 30ml of purified water at 5,10,20,30,40 and 50 min after capping;the rinsings were allowed to stand for 1 h and were subjected to OD determination at a wavelength of 541 nm.The above procedure was repeated twice,the average value of the twice experiments was taken for evaluation of the hemostatic effect of test product.For negative control group,all procedures except for capping were same as the test product group.The haemostatic effect was judged by percent OD relative to OD at 0 min in negative control group(OD 0 min)(OD 0 min was considered as 100%);if OD value at a time was less than 80% of OD 0 min,it should be designated as primary clotting time(PCT),less than 20% as complete clotting time(CCT).Results The measured PCT was 20min for both negative and positive control groups;CCT was 50,30 and 5 min for negative control,positive control and test product groups,respectively,showing the test styptic fiber had a CCT 8 times shorter than untreated blood,10 times shorter than negative control and 6 times shorter than positive control.Conclusions The test styptic fiber has powerful hemostatic effect.
2008年S1期 v.25 93页 [查看摘要][在线阅读][下载 12K] [下载次数：16 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：34 ] Objective To investigate the effect of muscone on cardiovascular system.Methods Experimental animals to divide muscone high、middle、low dose group(the mouse is 20 mg·kg-1,10 mg·kg-1,5.0 mg·kg-1;the rat is 10 mg·kg-1,5.0 mg·kg-1,2.5 mg·kg-1),GT group(the mouse is 1/12 mg·kg-1;the rat is 1/24 mg·kg-1)and NS group.Intragastric administration in a week,do the mouse ant-hypoxia experiment、the drug(Pit.)produce the rat myocardial ischemia experiment and obstruct coronary artery to produce the rat myocardial ischemia experiment.The mice's survival time(t),the rat's variation of T in electrocardiogram、creatinkinase(CK)and lactate dehydrogenase(LDH)were recorded,respectively.Results The effect of Muscone is significant difference between GT and NS in a dose variation manner.Conclusions Muscone has the effect of ant-hypoxia,cutting down T peak value,reducing CK and LDH.The muscone has effect to inhibiting myocardial ischemia.
2008年S1期 v.25 93-94页 [查看摘要][在线阅读][下载 23K] [下载次数：70 ] |[网刊下载次数：0 ] |[引用频次：3 ] |[阅读次数：58 ] -
Objective To investigate the effect of(-)-Stepholidine(SPD)on enhancing D1 receptor mediated contraction of cardiac muscle in isolated rat heart and to examine whether SPD has a direct effect on the heart dopamine D1 receptors.SPD an active ingredient of the Chinese herb Stephania intermedia,binds to dopamine D1 and D2 like receptors.Biochemical,electrophysiological and behavioural experiments have provided strong evidence that SPD is both a D(1/5)agonist and a D(2/4)antagonist,which could indicate unique antipsychotic properties.Methods Normal adult rat working hearts were isolated by Langendorff technique.Results SPD significantly increased the cardiac muscle contraction in a dose-dependent manner.The selective D1 dopamine receptor antagonist SCH23390(1 μM)blocked the SPD induced heart contraction,however,neither the β-receptor antagonist propranolol(1 μM)nor the α1-receptor antagonist prazosin(1 μM)had any effect on blocking SPD induced heart contractions.Moreover,the L-type Ca2+ channel inhibitor nimodipine(1 μM)completely blocked the effect of SPD on cardiac muscle contraction.Conclusions SPD show the effect on enhancing contraction of isolated rat heart through activating L-type Ca2+ channel mediated by heart D1 receptors.
2008年S1期 v.25 94页 [查看摘要][在线阅读][下载 11K] [下载次数：13 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：97 ] - tsuko Minobe;Masaki Kameyama;
Objective To explore the mechanism that cytoplasmic factors could recover L-type Ca2+ channel activity after "run-down".The factors include ATP,calpastatin and H fraction(a high molecular fraction of bovine cardiac cytoplasm).Methods Single Ca2+ channel activities were recorded with patch clamp technique in guinea-pig cardiac myocytes.Run-down was induced by the inside-out patch formation.Calpastatin(CS),calmodulin(CaM)and three GST-fusion fragment peptides derived from the C-terminal tail of guinea-pig Cav1.2,CT-1(amino acids number 1509-1791),CT-2(1777-2003)and CT-3(1944-2169)were produced as GST fusion proteins.Results(1)CaM + ATP or CS + ATP restored the channels after run-down;however,the CaM or CS's effects became smaller with the longer run-down time.(2)After run down,CaM-dependent protein kinase(CaMKII)produced Ca2+ channel activity to only 2-10% of the basal activity,however,in the presence of CaMKII,the time-dependent nature of the CaM effect was abolished.(3)In pull-down assay,CT-1 treated with CaMKII showed a higher affinity for CaM than that treated with phosphatase.(4)CaMKII was detected in the H fraction of bovine cardiac cytoplasm.Conclusions The results show that CS,CaM and CaMKII are all involved in the maintenance of the basal activity of L-type Ca2+ channels,and that there might be cross talks among the four factors(CS,CaM,CaMKII and the undefined cytoplasmic factor).
2008年S1期 v.25 94-95页 [查看摘要][在线阅读][下载 24K] [下载次数：56 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：69 ] -
Objective The experiment is to study the protective effects of Xinkang Injection on ADR-induced toxin myocarditisin mice.Methods The test of Xinkang Injection on ADR-induced toxin myocarditisin mice.Firstly,the animal of obnormal,weight and death rate.Secondly,the influnences of cardiogram of ADR-induced toxin myocarditisin mice.Thirdly,the influnences of lactate dehydrogenase(LDH),creatine kinase(CK)and glutamic oxaloacetic transaminasw(GOT)of ADR-induced toxin myocarditisin mice.Fouthly,the influnences of changes of cardioc pathological mechanism of ADR-induced toxin myocarditisin mice.Fifthly,the influnces of the caidioc ultrastructural of ADR-induced toxin myocarditisin mice.Results Firstly,to ADR-induced toxin myocarditisin mice,the weight of middle dose and high dose of Xinkang injection had declined obviosly which contrast with the constraction model mice team.In the mean time,the weight of Xinkang injection team had obviosly changde which contrast with contrastion mice team(P<0.01).Secondly,to ADR-induced toxin myocarditisin mice,the middle dose and high dose of Xinkang injection have obviosly withstand Q abnormal cardiogram,in the meantime,Xinkang injection team had obviosly changde contrast with the contrastion model mice(P<0.01).Thirdly,to ADR-induced toxin myocarditisin mice,The activity of lactate dehydrogenase(LDH),creatine kinase(CK)and glutamic oxaloacetic transaminasw(GOT)were differently measured.The middle dose and high dose of Xinkang injection team can obviously declined the activity of LDH and CK(P<0.01).Fouthly,to ADR-induced toxin myocarditisin mice,the low dose,the middle dose and high dose of Xinkang injection team can contrast with injured on toxic myocarditisin mice cardioc.Fifthly,to ADR-induced toxin myocarditisin mice,the low dose,the middle dose and high dose of Xinkang injection team have effect of allevite the injection of the cardioc ulteasteuctural of ADR-induced toxin myocarditisin mice.Conclusions Xinkang injection can protect the ADR-induced toxin myocarditisin mice.
2008年S1期 v.25 95-96页 [查看摘要][在线阅读][下载 23K] [下载次数：18 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：49 ] Objective To explore the new stratigies targeting at SUR2B/Kir6.1 subtype against pressure overload-induced heart failure.Methods Pressure overload-induced heart failure was induced in Wistar rat by abdominal aortic banding(AAB).The effects of natakalim(1,3,9 mg·kg-1·d-1,10 weeks)were assessed on myocardial hypertrophy and heart failure,cardiac histology,vasoactive compounds,and gene expression.Isolated working heart and isolated tail artery helical strips were used to examine the influence of natakalim on heart and resistant vessels.Results Ten weeks after the onset of pressure overload,natakalim therapy potently inhibited cardiac hypertrophy and prevented heart failure.Natakalim inhibited the changes of left ventricular haemodynamic parameters,reversed the increase of heart mass index,left ventricular weight index and lung weight index remarkably.Histological examination demonstrated that there were no significant hypertrophy and fibrosis in hearts of pressure overload rat treated with natakalim.Ultrastructural examination of heart revealed well-organized myofibrils with mitochondria grouped along the periphery of longitudinally oriented fibers in natakalim group rats.The content of serum NO and plasma PGI2 was increased,while that of plasma ET-1 and cardiac tissue hydroxyproline,ANP and BNP mRNA was down-regulated in natakalim-treated rats.Natakalim at concentrations ranging from 0.01-100 μM had no effects on isolated working heart derived from Wistar rats;however,natakalim had endothelium-dependent vasodilation effects on the isolated tail artery helical strips precontracted with NE.Conclusions These results indicate that natakalim improves heart failure due to pressure overload by activating KATP channel SUR2B/Kir6.1 subtype and reversing endothelial dysfunction.
2008年S1期 v.25 96-97页 [查看摘要][在线阅读][下载 21K] [下载次数：47 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：81 ] -
Objective To investigate the effects of prenatal exposure to lipopolysaccharide(LPS)on blood pressure and body weight of offspring in rats.Methods Sixteen healthy pregnant rats were randomly divided into two groups.The rats in LPS group were injected intraperitoneally with LPS(0.79 mg·kg-1)at the 8th,10th,12th day of gestation.Those in the control group were only treated with NS.After delivery,all offspring were weighed and blood pressure was measured by tail-cuff method once every two weeks from the 6th to 24th week.In the 15th week,their food intakes were weighed every day.At the end of the 24th week,the rats were put to death by decapitation.Abdominal adipose tissues were taken to weigh,and serum level of leptin was detected by RIA.Results The offspring with prenatal LPS exposure showed increased systemic arterial pressure,heavier body weight,elevated food intake,increased adipose tissue weight and increased circulating leptin compared with controls.Conclusions Prenatal exposure to LPS leads to increases in blood pressure and body weight in rats.
2008年S1期 v.25 96页 [查看摘要][在线阅读][下载 10K] [下载次数：18 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：49 ] - 刘明妍;魏敏杰;
目的研究健康中国男性志愿者口服10mg盐酸美金刚胶囊和片剂后的药代动力学和生物等效性。方法本实验研究采用单剂量、随机、开放、双周期的方法,在中国健康男性志愿者中进行研究。志愿者分别服用10mg单剂量的受试制剂或参比制剂,经过1周的清洗期后,再服药另一种药物。经过12小时禁食后,服用研究药物,在360h内的各个时间点分别抽取血样。药物的血药浓度用液质串联色谱(LC/MS)法测定。两种制剂的药动学参数Cmax,tmax,t1/2,AUC0-t,AUC0-∞可由血浆药物浓度计算而来。经过对数转换后Cmax,AUC0-t和AUC0-∞的可信区间在80%～125%之间时,认为两制剂生物等效。安全性评价用监测生命体征,实验室检查(血常规,血液生化,肝功和尿常规),和询问受试者的方法来评价。结果20名中国男性志愿者经过筛选后入选(平均值[标准差]:年龄为22.40[1.96]岁,体重为70.90[4.34]kg,身高为177.45[5.66]cm),并全部完成试验。美金刚受试制剂和参比制剂的主要药动学参数分别如下所示:Cmax(12.9[3.2],12.2[3.8])ng·mL-1;tmax(6.1[2.4],6.6[2.6])h;AUC0-t(902.4[291.6],845.1[255.7])ng·mL-1.h;AUC0-∞(977.0[328.7],932.7[261.6])ng·mL-1.h;t1/2(63.0[14.4],63.8[12.3])h。经过对数转换后Cmax,AUC0-t和AUC0-∞的90%置信区间分别为97.5～118.1,94.9～118.7和92.2～115.1。试验中无不良反应发生。结论在这个中国男性志愿者的小样本研究中,受试者单剂量口服10mg的美金刚胶囊(受试制剂)和美金刚片(参比制剂)具有生物等效性,并具有良好的耐受性。
2008年S1期 v.25 97页 [查看摘要][在线阅读][下载 10K] [下载次数：268 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：195 ] -
Objective To evaluate the pharmacokinetics(PK)properties and bioavailability of R-phencynonate(L-8021)in Beagle dogs.Methods Fifteen healthy Beagle dogs were randomly divided into three groups,each group was orally given single dose of 0.1 mg·kg-1,0.4 mg·kg-1 and 1.2 mg·kg-1 R-phencynonate respectively.After one week cleaning,the middle dose group was injected 0.4 mg·kg-1 dose.Blood samples(about 2 mL)were collected in heparinized tubes before dosing and at 0.033,0.083,0.25,0.5,0.75,1,2,4,6,8,12 h after administration,and were then immediately centrifuged at 2000 g for 15 min.The pharmacokinetics(PK)properties and bioavailability of the drugs was evaluated using the liquid chromatographic-tandem mass spectrometric(LC-MS/MS)method.Results After p.o.administration of 0.1,0.4 and 1.2 mg·kg-1 R-phencynonate,tmax ranged within 0.65-1.2 h;t1/2z ranged within 2.84-3.36 h;CLz/F ranged within 5.00-9.32 L·h-1·kg-1;Cmax ranged within 1.87-70.34 ng·mL-1;AUC(0-t)ranged within 9.80-250.12 μg·L-1·h;After i.v.administration of 0.4 mg·kg-1,t1/2z was 2.52 h;AUC(0-t)was 238.11 μg·L-1·h.Conclusions L-8021 was dose-dependent within the range of 0.1-1.2 mg·kg-1 in Beagle dogs and the blood drug concentration-time curves were all best fitted to first order absorption two-compartment open model after via po administration of three different dosages.Following oral administration to Beagle dogs,the absolute bioavailability of L-8021 was 17.82%,which was very low and resulted from poor absorption.
2008年S1期 v.25 98页 [查看摘要][在线阅读][下载 12K] [下载次数：24 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：41 ] Objective To evaluate the pharmacokinetics(PK)properties of extended release formulations of buspirone hydrochloride in Beagle dogs.Methods A randomized,two period,two treatment,two sequence crossover bioequivalence study was designed;six healthy Beagle dogs were randomly divided into two groups,each group was orally given buspirone tablets or buspirone extended capsule containing 15 mg buspirone hydrochloride.Blood samples(about 1 mL)were collected in heparinized tubes before dosing and at 0.33,0.67,1,2,3,4,6,8,10,12,18,24 h after administration,and were then immediately centrifuged at 3000 rpm for 15 min.The pharmacokinetics(PK)properties of the drugs were evaluated using the liquid chromatographic-tandem mass spectrometric(LC-MS/MS)method.Results The mean tmax was 4.7,0.8 h and Cmax values was 1.8,6.9 μg·L-1,respectively for the sustained-release test(capsule)and reference formulation(tablet).When compared to the tablets,the residence time of the sustained capsules was dramatically prolonged and Cmax was reduced(P<0.01).The initial release speed was slow and stable.The bioavailability was similar to the common tablets.Conclusions The sustained capsule had showed good pharmacokinetics property of sustained-release in the Beagle dogs.
2008年S1期 v.25 98-99页 [查看摘要][在线阅读][下载 25K] [下载次数：42 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：50 ] -
Objective To develop a simple and specific reversed-phase HPLC-UV method for simultaneous determination of(-)Epigallocatechin-3-gallate(EGCG)and(-)Epicatechin-3-gallate(ECG),the main active ingredients of tea polyphenols(TP),in rat plasma.Methods EGCG and ECG were eluted on a Kromasil C18 analytical column(150 mm×4.6 mm,5 μm)protected by a C18 pre-column(4.6 mm×20 mm,10 μm)with a linear gradient mobile phase composed of CH3CN(A)-0.1% citric acid(B),which was run from initial 14% A and 86% B to 20% A and 80% B at a flow rate of 1.0 mL·min-1 in 14 min,then changed to 14% A and 86% B at a gradient flow rate of 1.0-1.5 mL·min-1 during 14-18 min,and then maintained until 22 min at a gradient flow rate of 1.5-1.0 mL·min-1.The UV detector was set at 280 nm.Plasma samples(200 μL each)were prepared by liquid-liquid extraction procedure with double volumes of EtoAc and then evaporation of organic phase under N2 stream to dry,followed by reconstitution with 100 μL of 20% CH3CN aqueous solution.The peak area ratios of analytes to vanillin as internal standard vs concentration of analytes to construct calibration curves.Results The HPLC resulted in base-line separation of vanillin,EGCG,ECG and other components;there was no interference from blank plasma.The linear range was 0.5-300 μg·mL-1 for EGCG(r=0.9999)and 0.1-60 μg·mL-1 for ECG(r=0.9999).The intra-and inter-day precision(RSD)was better than 6.1% and 12.6%,respectively,and the average accuracy was between 86.25%-103.14%.The extraction recovery of EGCG and ECG was 79.80%-84.64% and 75.22%-91.39%,respectively.The plasma samples were stable for at least 30 days at-20 ℃ and 8 h at room temperature;EGCG,ECG and IS stock solutions 2 months at-20 ℃,and the EtoAc-extracted plasma samples 24 h at 4 ℃.Application of the method to the determination of EGCG and ECG in plasma of rats receiving iv 100 mg·kg-1 of TP showed that these 2 compounds pharmacokinetically behaved as the two-compartment model and first-order kinetics,with t1/2β 122.9 min and 59.2 min,Vd 7.96 L·kg-1 and 1.22 L·kg-1,CL 0.044 L·kg-1·min-1 and 0.015 L·kg-1·min-1 for EGCG and ECG,respectively.Conclusions The method developed in the present study is highly specific,precise,accurate,and suitable for the non-clinical pharmacokinetic study of the TP in rats.
2008年S1期 v.25 99页 [查看摘要][在线阅读][下载 13K] [下载次数：93 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：73 ] Objective Cyclo-trans-4-L-hydroxyprolyl-L-serine(JBP485)is a dipeptide isolated from Laennec,and Laennec is a hydrolyzate of human placenta.Evidence has indicated that JBP485 exhibited potent anti-hepatitis activity.In this study,we developed a method for rapid and sensitive determination of JBP485 in rat biologic samples by LC/MS,and then studied its pharmacokinetics.We investigated the main excretion pathway of JBP485.Methods Following protein-precipitation with methanol,the analyte and internal standard(Paracetamol)were separated from rat plasma using an isocratic mobile phase on an Cap cell pack C18 UG120 column with a mobile phase consisting of methanol-water-formic acid(30∶70∶0.2,V∶V∶V)at a flow rate of 0.5 mL·min-1.An API 3200 tandem mass spectrometer equipped with Turbo Ion Spray ionization source was used as detector and was operated in the positive ion mode.Multiple reaction monitoring transporter precursor to product ion combinations of m/z 201.1→86.1 and m/z 152.1→110.1 were performed to quantify JBP485 and internal standard,respectively.After JBP485 was injected intravenously at a dose of 25 mg·kg-1 to rats,blood,bile and urine was collected at different time up to 8 h.The plasma concentration-time curve was plotted.The main pharmacokinetic parameters of JBP485 were obtained by 3P97 software.Results Linear calibration was generated over a concentration range of 0.1-200 μg·mL-1 for biologic samples by using LC/MS,with the lower limit of quantification of 0.1 μg·mL-1.Intra-and inter-days precision and accuracy were acceptable for all quality control samples.The mean recovery of JBP485 was above 90%,respectively.Pharmacokinetic parameters were estimated as follows:AUC(9103.96±513.85)μg·min·mL-1,t1/2β(77.98±4.06)min and CL(0.002±0.0001)mL·kg-1·min-1.The cumulative urinary excretion for 8 hours after administration was 30% of the dose.The cumulative biliary excretion for 8 hours after administration was 2%.Conclusions The LC/MS method was suitable for the pharamacokinetic study of JBP485 in rat with the advantages of specificity,sensitivity,accuracy and high speed.Renal excretion was the main excretive route of JBP485.
2008年S1期 v.25 100页 [查看摘要][在线阅读][下载 11K] [下载次数：94 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：52 ] -
Objective To study pharmacokinetics of the main active ingredients(-)Epigallocatechin-3-gallate(EGCG)and(-)Epicatechin-3-gallate(ECG)of tea polyphenols(TP)injection in rats.Methods EGCG and ECG in rat plasma were analyzed by reversed-phase HPLC,by which EGCG and ECG were eluted from a Kromasil C18 column with a linear gradient mobile phase consisting of CH3CN-0.1% citric acid at a gradient flow rate of 1.0-1.5 mL·min-1 and monitored at a wavelength of 280 nm.Fifteen rats were randomly divided into 3 groups of 5 animals receiving iv administration of TP injection,formulated with catechins-containing extract from green tea,at doses of 150,100 and 50 mg·kg-1,respectively.Blood samples were collected pre-dosing and 2,5,10,20,40,60,90,120,180,240,300 min postdosing.Aliquots of obtained plasma(200 μL)were cleaned up by liquid-liquid extraction with double volumes of EtoAc and were reconstituted with 100 μL of 10% CH3CN aqueous solution before injecting to chromatograph.Results The time course of EGCG and ECG concentrations in rat plasma decayed in a biexponential fashion.Their iv pharmacokinetics could be described by the two-compartment model and first-order kinetics with t1/2β 112.39-145.20 min and 46.63-61.48 min,Vd 6.28-7.96 L·kg-1 and 0.90-1.22 L·kg-1,CL 0.034-0.044 L·kg-1·min-1 and 0.010-0.015 L·kg-1·min-1 for EGCG and ECG,respectively.Conclusions The EGCG and ECG in plasma of rats administered i.v.TP injection pharmacokinetically behaved with linear kinetics over dose range studied.The two catechin derivatives undergo rapid elimination from rat body.As compared with ECG,EGCG eliminates at a relatively slow rate,and is distributed very widely with a Vd greatly exceeding the volume of total body water,suggesting that EGCG is likely to enter the tissue cells or strongly bind to some tissues to exert its potent antioxidant effects.The aforementioned characteristics of EGCG may be due to its high lipophilicity.
2008年S1期 v.25 100-101页 [查看摘要][在线阅读][下载 25K] [下载次数：57 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：48 ] Objective To compare the pharmacokinetics of Alprazolam after intranasal and intragastic administration in rats and evaluate the practicability of Alprazolam as a nasal drug delivery system.Methods 12 rats were randomly divided into two groups.The fate of drug in the serum of rats was monitered after intranasal and intragastic administration of Alprazolam 2 mg·kg-1.Serum levels of Alprazolam were determined by reversed-phase HPLC with Diode array detectors(DAD).Chromatographic conditions were adopted with ODS column as solid phase,methanaol-0.02 M ammonium acetate(pH=5.0)(60∶40)as mobile phase at a flow rate of 1.0 mL·min-1.The detection wavelength was 223 nm.The concentration-time data were analyzed using 3P87 program,and the pharmacokinetic parameters were compared by t-test.Results The pharmacokinetic characteristics were fit to two and one compartment opened model after intranasal and intragastic administration of Alprazolam,respectively.The drug absorption was quicker and the serum concentrations of Alprazolam was significantly higher in rats after intranasal administration group than that intragastic administration group(P<0.05).The eliminate parameters between the two groups were no significant difference(P>0.05).Means of pharmacokinetic parameters in intranasal and intragastic groups were:Ka 37.35±22.98 vs 11.57±12.47 h-1(P<0.05),t1/2ka0.025±0.013 vs 0.156±0.122 h(P<0.05),β(Ke)0.3131±0.1194 vs 0.3091±0.1216 h-1(P>0.05),t1/2β(t1/2Ke)2.51±0.99 vs 2.54±0.97 h(P>0.05),tmax 0.156±0.069 vs 0.618±0.414 h(P<0.01),Cmax 353.11±96.30 vs 62.09±35.08 μg·L-1(P<0.01),AUC 1111.6±473.2 vs 274.1±185.3 μg·L-1·h(P<0.01).Conclusions Alprazolam was absorbed quickly in rats after intranasal administration.And the serum concentration and bioavailability can be significantly increased after intranasal administration,which may be an effective preparation as nasal drug delivery system.
2008年S1期 v.25 101-102页 [查看摘要][在线阅读][下载 24K] [下载次数：43 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：52 ] -
Objective To determine whether the cytochrome P4502B6(CYP2B6)is involved in the oxidation of propofol by human liver microsomes.Methods The change of propofol concentration in an incubation mixture with human liver microsomes was monitored by the high performance liquid chromatography(HPLC),in order to calculate the rate constants of metabolism of propofol.The correlation between the rate constants and the rate of metabolism of CYP2B6 selective substrate bupropion,and the effect of two different CYP2B6 specific inhibitors on the propofol metabolism were examined.Results The mean rate constant of propofol metabolism by liver microsomes obtained from twelve individuals was 3.9(95% confidence intervals 3.3,4.5)nmol·min-1·mg-1 protein.The rate constants of propofol metabolism by liver microsomes were significantly correlated with bupropion hydroxylation(r=0.888,P<0.001).Both selective chemical inhibitors of CYP2B6,orphenadrine and N,N',N″-triethylenethiophosphoramide(thioTEPA),reduced the rate constants of propofol metabolism by 37.5%(P<0.001)and 42.7%(P<0.001)in liver microsomes,respectively.Conclusions CYP2B6 is predominantly involved in the oxidation of propofol by human liver microsomes.
2008年S1期 v.25 102页 [查看摘要][在线阅读][下载 11K] [下载次数：46 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：79 ] Objective To evaluate the bioavailability and bioequivalence of oseltamivir capsule in Chinese health male volunteers.Methods A randomized,two period,two treatment,two sequence crossover bioequivalence trial was designed,24 Chinese health volunteers were randomly divided into two groups,each group was orally given single dose oseltamivir phosphate(tamifla)or AMMS 607 capsule.The active metabolite oseltamivir carboxylate of oseltamivir in the plasma were determined by liquid chromatographic-tandem mass spectrometric(LC-MS/MS)method.The pharmacokinetics parameters and relative bioavailability were calculated to evaluate the bioequivalence of AMMS 607 and tamifla.Results Cmax of the AMMS 607 and tamifla were 602.07±153.27 ng·mL-1 and 620.09±132.39 ng·mL-1 respectively;tmax were 4.2±1.1 h and 4.8±1.0 h;t1/2β were 6.60±0.87 h and 6.61±0.83 h;MRT were 10.00±1.77 h and 10.40±1.62 h;AUC0-24 were 6285.88±1083.66 ng·h·mL-1 and 6546.01±1199.32 ng·h·mL-1;Compared with the reference of tamifla capsule,the bioavailability F0-tn of AMMS 607 capsule was 99.5±27.7%.The main pharmacokinetics parameters of AUC0-24,Cmax and Tmax showed no statistically significant difference between the two capsules.Conclusions The AMMS 607 capsule and tamifla capsule are bioequivalent.
2008年S1期 v.25 102-103页 [查看摘要][在线阅读][下载 24K] [下载次数：82 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：78 ] -
Objective To contrast the roles of Asparagus officinalis polysaccharide on erythrocyte of S180 mice played in immunological reaction of lymphocytes.To study the effect of Asparagus officinalis polysaccharide on the erythrocyte function of S180 mice.Methods Suspensions of lymphocytes(1×106/mL)and autologous plasma were respectively separated from anticoaguted whole blood of healthy mice with the lymphocyte separation medium.The erythrocytes(1×108/mL)were separated from whole blood of Asparagus officinalis polysaccharide mice.Using the autologous plasm as reactive medium,the role of erythrocytes in regulating the immunological reaction of lymphocytes was appraised.The expression of CD25 on lymphocytes was detected using flow cytometry.Results The immunogical regulating ability of erythrocyte in mice with control groups is much lower than that of normal groups,and the immunogical regulating ability of erythrocyte in mice with Asparagus officinalis polysaccharide groups is much higher than that of control groups.Conclusions According to the effects of erythrocyte CD35 on the immuno-response of lymphocyte and the different of the expression of CD25 on lymphocytes,we prove that Asparagus officinalis polysaccharide can improve the erythrocyte function of S180 mice.
2008年S1期 v.25 103页 [查看摘要][在线阅读][下载 13K] [下载次数：43 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：64 ] Objective To investigate the effect of XBXT-2 on the activity of hypothalamic-pituitary-adrenal(HPA)axis in chronic mild stress(CMS)model of rats.Methods Using ELISA to test the serum corticosterone,adrenocorticotropic hormone(ACTH)and corticotropin-releasing hormone(CRH)level in CMS rats;Using western blot to determine hippocampal glucocorticoids receptors(GR)expression in CMS rats.Results Co-administration of XBXT-2(25,50 mg·kg-1,p.o.,28 days,the effective doses for behavioral responses)significantly decreased the serum corticosterone and ACTH level in CMS rats,while the CRH level was not markedly affected by chronic stress or drugs.Moreover,XBXT-2 significantly increased the GR expression in the hippocampus of CMS rats.The same effects were observed in the positive control drug imipramine(10 mg·kg-1,p.o.).Conclusions The decrease of serum corticosterone and ACTH level,as well as the increase of hippocampal GR expression may be the mechanisms underlying the antidepressant action of XBXT-2,which may associate with HPA axis.
2008年S1期 v.25 104页 [查看摘要][在线阅读][下载 10K] [下载次数：35 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：71 ] -
Objective To investigate the anti-inflammation effect and possible mechanism of Salvianic acid A(SAA)in mouse peritoneal macrophages.Methods Peritoneal macrophages were obtained from BALB/c mice.LPS induced nitric oxide(NO),tumor necrosis factor-alpha(TNF-α)and interleukin-6(IL-6)in supernatant,protein expression of inducible nitric oxide synthase(iNOS),matrix metalloproteinase-9(MMP-9)and activation of nuclear factor-kappa B(NF-κB)in the extract were measured.Results SAA strongly inhibited the excessive production of NO,TNF-α and IL-6 in LPS-induced peritoneal macrophages in a concentration-dependent manner and blocked the expression of iNOS and MMP-9.Treatment with LPS alone increased the translocation of NF-κB(p65)from cytosol to the nucleus,but the SAA inhibited the translocation of NF-κB(p65).Conclusions The results showed that SAA had strong anti-inflammatory effects in LPS-stimulated peritoneal macrophages.The important mechanism is due to its inhibition of NF-κB activation.
2008年S1期 v.25 104-105页 [查看摘要][在线阅读][下载 21K] [下载次数：22 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：45 ] Objective To study the relaxant effect mechanism of an estrone derivate EA303 on isolate colonic smooth muscle of rabbits.Methods Preparations of the isolated colonic smooth muscle of rabbits were prepared.The effect of EA303 on potassium channel,β receptor and prostaglandin were studied by observing the difference of relaxant dose-effect curves of EA303 on preparations pre-contracted with BaCl2,High K+ solution and Acetylcholine chloride(ACh)in the absence or presence incubation with glibenclamide(10 μM),propranolol(0.1 μM)and Indometacin(10 μM).Results The relaxant effect of EA303 on contraction caused by BaCl2 and High K+ solution were weakened by glibenclamide inhibiting the opening of K+ channel while the relaxant effect of that on contraction caused by ACh was strengthened,after adding propranolol inhabiting β receptor,EA303 attenuated the relaxant action on contraction caused by BaCl2.EA303 had some relaxant impact on contraction induced by High K+ solution after adding indometacin inhabiting the synthesis the prostaglandin(PG).Conclusions The relaxant effect of EA303 on isolated colonic smooth muscle of rabbits may be related with PG synthesis enzyme,potassium channel and β receptor.
2008年S1期 v.25 105-106页 [查看摘要][在线阅读][下载 19K] [下载次数：18 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：35 ] -
Objective To study the anti-inflammatory effect of a poly-prescription of traditional Chinese medicine GK001.Methods 1.Inhibitory effect on pain in mice:The pain was induced by i.p.0.2 ml of 0.6% HAc per mouse 1 h post dosing GK001.The writhing numbers of mice were recorded in 10 minutes and the inhibitory rate of pain was calculated compared with the control group.2.Antipyretic effect In single dose experiment 15 healthy rabbits weighing 1.7-2.8 kg with body temperature(BT)measured in the experiment day meeting to the requirements were selected for the experiment and divided into 5 groups(3 in each group),which were dosed orally with GK001 and 1 h later followed by i.p.injection of 40 EU bacterial endotoxin standard·kg-1.Then,the BT of rabbits was measured every 30 min during 1-3 h after administration.The difference between the highest BT post-dose and the average BT pre-dose was calculated.In multi-dose experiment rabbits were selected and grouped as well as received i.p.endotoxin in the same way as above,but were administered with GK001 for consecutive 5 day.3.Bacteriostatic effect.The antibacterial activities of GK001 on Bacillus Pumilus,Bacillus Subtilis and Micrococcus Luteus were measured in vitro at concentrations of 0.125-1.0 g·mL-1.Results 1.The GK001 showed a significant and dose-dependent pain-suppressant effect,with inhibitory rate being 45.2%,31.2% and 20.8% at high,medium and low dose,respectively(P<0.05).2.Both single and multiple administration of GK001 had no effect on rabbit pyrogen response caused by endotoxin.3.GK001 had bacteriostatic effects on the aforementioned 3 bacteria significantly and in dose-dependent fashion.Conclusions GK001 has analgesic and in vitro antibacterial but no antipyretic effects.
2008年S1期 v.25 105页 [查看摘要][在线阅读][下载 11K] [下载次数：38 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：50 ] - 孙明立;魏敏杰;金万宝;杜娃;王爽;赵琳;赵海山;姚维凡;
目的探讨卡介菌多糖-核酸对二硝基氟苯诱导的接触性皮炎的治疗作用,并探讨其可能的作用机制。方法利用二硝基氟苯诱导建立小鼠接触性皮炎动物模型。激发后48小时,肌肉注射卡介菌多糖-核酸。给药期间,隔日1次对激发部位进行评分,末次给药后24小时,取激发部位皮肤进行病理学观察,取外周血ELISA法检测血浆中IL-2,IL-4andIFN-γ水平,流式细胞术检测外周血中T淋巴细胞亚群的百分比。结果治疗作用研究结果表明:卡介菌多糖-核酸可剂量依赖性缓解二硝基氟苯诱导的小鼠接触性皮炎的症状,减少激发部位皮肤中炎症细胞的数目。作用机制研究结果表明:卡介菌多糖-核酸可剂量依赖性减少外周血中IL-4水平,增加IL-2和IFN-γ水平,增加外周血中CD4+T细胞百分比及CD4+T细胞与CD8+T细胞百分比的比值。结论卡介菌多糖-核酸有望成为一种有效的治疗接触性皮炎的药物,其作用机制可能与它调节T淋巴细胞亚群和细胞因子失调有关。
2008年S1期 v.25 106页 [查看摘要][在线阅读][下载 8K] [下载次数：135 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：96 ] - 孙明立;魏敏杰;金万宝;王麟;戚勋;赵琳;
目的研究卡介菌多糖-核酸(BCG-PSN)的抗I型过敏反应作用,并探讨其可能的作用机制。方法建立卵白蛋白致敏大鼠血清引起的大鼠同种被动皮肤过敏反应(PCA)模型、磷酸组胺诱导的大鼠皮肤血管通透性升高模型、低分子右旋糖酐诱导的小鼠全身皮肤瘙痒模型,探讨BCG-PSN在体抗I型过敏反应作用;卵白蛋白致敏大鼠腹腔肥大细胞主动脱颗粒试验法探讨BCG-PSN离体抗I型过敏反应作用;ELISA法检测外周血中IL-4、IFN-γ水平和IgE抗体滴度,探讨BCG-PSN抗I型过敏反应可能的作用机制。结果大鼠隔日肌内注射BCG-PSN(0.026,0.077,0.232mg·kg-1)3wk、小鼠隔日肌内注射BCG-PSN(0.025,0.075,0.225mg·kg-1)3wk,均可剂量依赖性抑制卵白蛋白诱导的大鼠PCA,缓解低分子右旋糖酐诱导的小鼠全身皮肤瘙痒,对磷酸组胺诱导的大鼠皮肤血管通透性增高无影响;BCG-PSN(10-6mg·mL-1～10-3mg·mL-1)可浓度依赖性抑制卵白蛋白诱导的肥大细胞脱颗粒反应,最大抑制率为69.12%,抑制肥大细胞脱颗粒反应的半数抑制浓度(IC50)为7×10-5mg·mL-1;与生理盐水对照组比较,BCG-PSN三个剂量组1∶2、1∶8、1∶32三个血清稀释度蓝斑平均OD值均明显降低(P<0.05),外周血中IL-4水平明显降低(P<0.05),IFN-γ水平明显升高(P<0.05)。结论BCG-PSN可剂量依赖性抑制I型过敏反应作用,其抗I型过敏反应的可能机制与抑制血清IgE的生成,减少外周血中IL-4水平,增加外周血中IFN-γ水平有关。
2008年S1期 v.25 106-107页 [查看摘要][在线阅读][下载 17K] [下载次数：144 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：112 ] - 贺素荣;狄安稞;白雪峰;魏敏杰;
目的调查哮喘大鼠肺泡巨噬细胞IL-6和TNF-αmRNA表达水平的变化及其在哮喘发病中的作用。方法利用卵蛋白(ovialbumin,OVA)致敏并激发大鼠建立哮喘模型,对照组则用生理盐水代替;收集支气管肺泡灌洗液(bronchusalveolar lavage fluid,BALF)并用RMPI1640培养AM。各组细胞在利用LPS(5μg.ml-1)处理12小时前后,通过RT-PCR技术检测肺泡巨噬细胞中IL-6和TNF-αmRNA的表达水平。结果病理学检测发现哮喘模型组(n=7)炎症细胞浸润明显增加,支气管肺泡灌洗液(BALF)细胞总数显著增高,与对照组(n=7)比较差异显著(P<0.01)。两组肺泡巨噬细胞经LPS处理后,IL-6和TNF-αmRNA的表达水平明显增高(n=7,P<0.01)。无论LPS处理与否,哮喘组肺泡巨噬细胞IL-6的表达水平与对照组相比明显增高(n=7,P<0.01);TNF-α的表达水平变化情况与IL-6相似,但其显著性不及IL-6高(n=7,P<0.05)。结论哮喘大鼠肺泡巨噬细胞IL-6和TNF-αmRNA的表达水平与对照组相比明显增高。由此可见,哮喘大鼠的肺泡巨噬细胞被激活并且产生IL-6和TNF-α从而参与哮喘的发生发展。
2008年S1期 v.25 107页 [查看摘要][在线阅读][下载 9K] [下载次数：162 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：128 ] -
Objective To study the effects and mechanisms of scopolin isolated from the stems of Erycibe obtusifolia Benth in arthritis-associated inflammation and angiogenesis.Methods Adjuvant-induced arthritic rat,an animal model for human RA was used in this study for examining the potential remedial effect of scopolin.The swelling in both inoculated and non-inoculated paws,body weights and articular index(AI)scores were detected to evaluate the severity of the arthritis.Histologic assessment of tissue sections from rat ankles was also performed.Furthermore,the blood vessel density in the synovial tissues was quantitatively evaluated.In addition,expressions of VEGF,FGF-2,TNF-α,IL-1β and IL-6 in rat synovial tissues were determined by immunohistochemistry assay in an attempt to explain the mechanisms of scopolin for suppressing arthritis.Results Scopolin dose-dependently inhibited both inoculated and non-inoculated paw swelling in rat AIA.The mean AI scores of scopolin treated groups were also dose-dependently lower than that of model group.In addition,compared with the weights of model group,the mean body weights of rats treated with scopolin(50,100 mg·kg-1)were higher from day 13 to 22,perhaps indicative of healthier animals.The histologic architecture of the joint was highly abnormal in the model group rats,while high dose of scopolin treated rats preserved a nearly normal histologic architecture of the joint.Moreover,the new blood vessels were reduced dose-dependently in the synovial tissue of rat AIA treated with scopolin.Further,scopolin reduced the overexpression of IL-6,VEGF and FGF-2 in rat synovial tissues.Conclusions Scopolin is capable of reducing clinical symptoms of rat AIA by inhibiting inflammation and angiogenesis,and this compound may be a potent therapeutic agent for angiogenesis related diseases and can serve as structural base for screening for more potent synthetic analogs.
2008年S1期 v.25 107-108页 [查看摘要][在线阅读][下载 23K] [下载次数：39 ] |[网刊下载次数：0 ] |[引用频次：1 ] |[阅读次数：36 ] Objective To investigate the effect of Xiaofenghuoxue decotion(XFHX)on the production of Th1 and Th2 cytokine in bronchoalveolar lavage fluid(BALF)in asthma guinea pigs sensitized and challenged with ovalbumin.Methods The animals were randomly divided into 5 groups:the normal control group,the asthma group,the XFHX high dose group,the XFHX low dose group and the budesonide group.2 weeks after sensitization with a mixture of 10% OVA and 10% Al(OH)3,the drugs were given to the animals for 7 days,and then the animals were challenged with aerosol of 1% ovalbumin,the latency time for the onset of respiratory abnormalities was examined,BALF was collected 16 h after.Leukocyte in BALF was counted.The level of IFN-γ reduced by Th1 cells and IL-4 and IL-5 produced by Th2 cells were determined by EILSA.NO contents were also examined.Results The latency time for the onset of respiratory abnormalities and leukocyte infiltration in both XFHX high dose group and low dose group significantly decreased compared with the asthma group.The level of IFN-γ in both XFHX high dose group and low dose group significantly increased compared with the asthma group,the level of IL-4 and IL-5 in both XFHX high dose group and low dose group significantly decreased compared with the asthma group.The production of NO was inhibited in both XFHX high dose group and low dose group compared with the asthma group.Conclusions These results suggest that the anti-asthma effect of Xiaofenghuoxue decotion is associated with NO regulated reversal of Th1/Th2 cytokine balance in allergen-induced asthma guinea pigs.
2008年S1期 v.25 108-109页 [查看摘要][在线阅读][下载 23K] [下载次数：26 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：51 ] -
Objective Essential hypertension(EH)is one of the most common cardiovascular disease and the main causes of human fatility.Recently significant progress has been made in our lab,it was found that exterior stimulation during pregnancy may play a key role in chronicle adult disease.However,what factors affect the growth of fetus after those exterior stimulation and why has not been reported.Based on our previous finding,this study intends to investigate how immuno-inflammatory stimulation affect the development of embryo.Methods 1.Sprague-Dawley(SD)rats,dams in each group received i.p.injections of 0.79 mg·kg-1 LPS,8 mg·kg-1 zymosan or sterile saline respectively on their gestational days 8,10,and 12.2.The serums were collected in tail nick at 2 h after the last injection,and the amniotic fluid was mixed at 2,12,24,48 h after the last injection.TNF-α and IL-6 levels of serum and amniotic fluid were measured by RIA method.3.TNF-α and IL-6 mRNA levels were quantitated in amnion,placenta,amniotic fluid,Embryo and macrophage by real-time fluorescent quantitative-PCR.Results 1.The serum level of TNF-α and IL-6 in LPS group and zymosan group was higher than that in control group(P<0.01).It showed that there was immuno-imflammatory response after LPS or zymosan injection in rats.The mRNA levels of TNF-α and IL-6 was very higher in macrophage than in other organization.2.In embryo,the mRNA level of IL-6 was more than other organization,but the mRNA level of TNF-α was lower than other organization.However,the IL-6 mRNA level of LPS group and zymosan group was higher several dozens times than control group on 24 h and 48 h.Conclusions It suggested that IL-6 was important in the model that prenatalexposure to immuno-inflammatory stimulant results in increases of blood pressure and body weight in rats.
2008年S1期 v.25 109-110页 [查看摘要][在线阅读][下载 23K] [下载次数：23 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：45 ] Objective To explore the roles of IH 901 on the formation of foam cell sourced from rat peritoneal macrophage.Methods The cultured rat peritoneal macrophages were incubated with ox-LDL to get foam cell as model group.Different doses of IH 901 were added into the culture medium(10 μM,25 μM,50 μM).Foam cell was stained by oil red O.The content of total cholesterol and cholesterol ester were examined to show the formation of foam cells.And the concentrations of TNF-α and IL-1 in culture supernatant were detected.The expression of NF-κB,perilipin and CD36 were measured by western blotting.Results Compared with model group,the formation of foam cell was significantly reduced by IH 901 treatment(50 μM,25 μM),while the amount of living cells of 50 μM group was lessened compared with other groups.Compared with model group,the contents of total cholesterol,cholesterol ester and CE/TC ratio were significantly reduced in IH 901 50 μM and 25 μM groups(P<0.05).Meanwhile,there was obvious difference among IH 901 groups.The concentrations of TNF-α and IL-1 in IH 901 high and middle dose groups were reduced remarkable compared with model group.The changes of expression of NF-κB,perilipin and CD36 showed the similar tendency of the results above.There were no noticeable difference between model group and IH 901 low dose group.Conclusions IH 901 could reduce the formation of foam cell sourced from rat peritoneal macrophage dose dependently.The mechanism may depend on the effects of IH 901 reducing the inflammation reaction of macrophage and the expression of perilipin.
2008年S1期 v.25 109页 [查看摘要][在线阅读][下载 9K] [下载次数：18 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：37 ] -
Objective To study the molecular biology mechanism of Danggui-buxue-tang on tonifying Qi and controlling blood circulation through modulation the immune functional genes.Methods Rats were randomly divided into control group,model group,and Danggui-buxue-tang group.Effect of Dang-guibuxue-tang on mRNA expressions of IL-1β,TNF-α,HSP-70,NF-κB,p38MAPK and JNK in blood cells of rats with Qi deficiency and blood stasis were measured with real-time fluorescent quantitative-PCR at 5th,14th and 28th day.And that in artery wall were determined at the 28th day.NF-κB/p65 and p-c-jun protein expressions in rat artery wall were detected by western blotting as well.Results In model group,TNF-α,IL-1β,NF-κB,HSP-70,p38MAPK and JNK mRNA expression in blood cell increased significantly compared with control group.Compared with model group,mRNA expression of IL-1βand JNK decreased significantly;TNF-α decreased at 5th,14th day;HSP-70,p38MAPK decreased at 14th,28th day;NF-κB decreased at 28th day.In model group,TNF-α,IL-1β,NF-κB,p38MAPK and JNK mRNA expression in artery increased compared with control group,excluded HSP-70,and that in Danggui-buxue-tang group decreased significantly.In model group,NF-κB/p65 and p-c-jun protein expression in artery increased compared with control group,and that in Danggui-buxue-tang group decreased significantly.Conclusions The effects of Dang-guibuxue-tang on Qi deficiency and blood stasis syndrome was brought from the regulating of cytokine network at multi-link and multi-target,NF-κB,p38MAPK and JNK signal transduction pathways included.Through which the immune system and whole body reached to a functional balance status.
2008年S1期 v.25 110-111页 [查看摘要][在线阅读][下载 24K] [下载次数：34 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：39 ] Objective To establish a rat model of sterility associated with epididymis and epididymal gene expression profiles relation to fertility by alpha-chlorohydrin.Methods Rats were treated with 10 mg·kg-1·d-1.alpha-chlorohydrin for 10 consecutive days.Sperm maturation and other fertility parameters were analyzed.The sperm motility and morphology were evaluated by computer-assisted sperm analysis(CASA);sperm survival rate was assessed by SYBR-14 and propidium iodide(PI)fluorescent staining;the weights of testes,epididymides,prostates and seminal vesicles were determined by electronic balance;histological examination of above tissues were evaluated by HE staining;and serumal dihydrotestosterone(DHT)and testosterone(T)of rats were detected by enzyme-labeled immunoassay.Each male rat was paired with 2 female rats in proestrus.Female rats were examined the next morning for the presence of sperm in vaginal smears and underwent a cesarean section on day 12 of gestation.Finally the reproductive indices were calculated as follows:copulation index(number of sperm positive females /number of pairings),pregnancy index(number of pregnancies /number of sperm positive females),and fertility index(number of pregnancies /number of pairings).After that we used Affymetrix Rat 230 2.0 oligo-microarray to identify epididymal special genes associated with fertility.Finally,we validated some of these genes by Real-Time quantitative polymerase chain reaction.Results The motility of spermatozoa from the cauda epididymidis of treated rats showed a significant decrease in percentage of motile,progressively motile sperm,and sperm survival rate.At the same time,the morphology of cauda epididymal spermatozoa was also adversely affected by the treatment.In addition,the serumal androgen levels of treated animals weren't changed compared with the control group.Accordingly,matings with treated males resulted in no successful pregnancy.Then,we classified general functions of the down or up regulated epididymal genes by chlorhydrin with the GeneSpring gene ontology(GO)analysis,which are involved in macromolecular metabolism and transport,primary metabolism process,cell metabolism,biological process regulation,immunology regulation,ion combination,hydratase and oxidoreductase activity.Among all the different expressed genes,we analyzed and screened the down-regulated genes associated with glucose,lipid,protein and other energy metabolism,which are considered as the major ACH action targets.Simultaneously,the up-regulated genes by chlorhydrin were detected and their characters of negative regulated sperm maturation and fertility analyzed,which are apoptosis and immune-related genes and not reported before.Conclusions We established male infertile rat model with ACH(10 mg·kg-1·d-1,po,10 days)through evaluating changes of sperm motility and morphology,mating index,fertility index and pregnancy index.Simultaneously,the ACH didn't affect the major androgen(T and DHT)metabolism and sexual ability,which is considered as the best way for male contraception.Then we determined the down-regulated epididymal genes relation to substance metabolism,which can affect the epididymal sperm maturation and presumed the major antifertility targets by ACH.Further more,we found and analyzed the epididymal up-regulated genes associated with apoptosis and immune functions,which maybe the new possible sites of action by ACH and other male antifertility agents.
2008年S1期 v.25 111-112页 [查看摘要][在线阅读][下载 24K] [下载次数：16 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：43 ] -
Objective To investigate the effect of astragaloside(AST)on the gastric mucosal injury of water immersion restraint stress ulcer rat.Methods The stress ulcer model was made by water immersion and restraint.The gastric mucosal injury index was observed.The SOD activity,the MDA contents and the gene expression of melatonin receptor 1 and 2 were detected in gastric mucosa.Results Compared with the normal group,the model group showed mucous edema,hyperemia and even ulcer damage.The injury index and the MDA content of gastric mucosa in model group were significantly increased(P<0.05),the SOD activity of gastric obviously depressed(P<0.01),and the melatonin receptor 1 and 2 mRNA expressions of damaged gastric mucosa were also lower.After administration of AST,the gastric mucosal ulcer index and MDA contents relieved obviously(P<0.01,P<0.05),the SOD activity and the expressions of melatonin receptor 1 and 2 mRNA raised up(P<0.01,P<0.05).Conclusions AST could prevent the gastric mucosal damage of rat in stress ulcer.And the mechanism of the gastric mucosal protection should be concerned with regulating the melatonin receptor and lessening the injury of oxygen free radical.
2008年S1期 v.25 111页 [查看摘要][在线阅读][下载 10K] [下载次数：35 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：53 ] - 聂宏光;韩冬云;吉宏龙;李金鸣;
目的探讨钾通道在维拉帕米引起的肺水肿中的作用。方法应用尤斯灌流室技术检测钾通道阻滞剂对维拉帕米抑制上皮钠通道的作用。Clofilium,clotrimazole以及glibenclamide(分别为KvLQT1,KCa和KATP通道的阻滞剂)加入H441单层细胞基底侧后,记录短路电流。同时,在穿孔细胞层中观察了维拉帕米对Na+/K+泵的作用。结果在穿孔H441细胞层中观察到维拉帕米对上皮钠通道和Na+/K+泵均有抑制作用。Clofilium,clotri mazole以及glibenclamide分别抑制短路电流至54.4±4.6%,32.1±5.2%,和20.5±1.1%(n=5)。用上述三种钾通道阻滞剂预处理后,维拉帕米对短路电流的作用由对照组的45.9±4.8%分别降低至23.7±4.3%,34.2±2.6%和36.0±2.8%(n=4)。Clofilium显示了对短路电流的最大抑制,与其它两种抑制剂相比具有统计学差异。应用clofilium后加入维拉帕米与对照组相比,其抑制率具有明显统计学差异(P<0.05)。结论这些结果表明KCa,KATP,尤其是KvLQT1通道在肺上皮细胞维拉帕米引起的非心源性肺水肿的Na+和Cl-转运的病理生理过程中发挥重要作用。
2008年S1期 v.25 112-113页 [查看摘要][在线阅读][下载 24K] [下载次数：144 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：93 ] -
Objective To inspect the effect of Sachalin rhodiola rhizome extract to the swimming time and content of liver starch and liver cells morphous of sports fatigue rat.Methods Using weight loading swimming to determine swimming time,using kits to determine liver starch,using transmission electron microscope to observe the diversify of rat liver cells morphous and construction.Results To compare with negative control group,the Sachalin rhodiola rhizome extract can obviously extend survival time of swimming rat,increase the content of liver starch.Conclusions Sachalin rhodiola rhizome extract can raise the staying power of sports fatigue rat,strengthen sport ability and play a part in antifatigue by increasing the content of liver starch and protecting liver cells of sports fatigue rat.
2008年S1期 v.25 113页 [查看摘要][在线阅读][下载 10K] [下载次数：28 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：76 ] Objective To observe the prevention and therapeutic effects of tanshitone(TAN)on retinoic acid induced osteoporosis in mice.Methods The mice osteoporosis was induced by given retinoic acid intragasttrically for two weeks.The histomorphological features of bone were observed and biochemical indexes in serum(Ca,P,ALP,TRAP,E2,BGP)were determined after mice were given TAN at the dose of 40,80,160 mg·kg-1 respectively.Results Tanshitone can induce high conversion of osteoporosis.The levels of P,ALP,TRAP and BGP in the TAN groups were lower than the model group,while the E2 level was higher than the model group.Conclusions Tanshitone can prevent the loss bone in the experimental mice.The mechanism may be that it improves the level of estrogenic hormone and inhibits the high bone turnover.
2008年S1期 v.25 113-114页 [查看摘要][在线阅读][下载 21K] [下载次数：35 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：70 ] -
Objective To evaluate and analyze the preventive and therapeutic effects of Gushudan on osteoporosis in rats after administrated prednisolone and investigate the mechanisms by study Osteoblast-like cells.Methods 60 Wistar male rats were divided into 6 groups:normal control group,model control group,Gushudan Prescription groups of 3,1,0.3 g/kg dose,Gushukang 1 g·kg-1 group.The effect was observed by measuring the levels of blood calcium,blood phosphorus,blood BGP content,bone calcium,bone phosphorus,bone density and bone biomechanics.Results After 8 weeks,Gushudan significantly increases the bone density,bone biomechanics,blood BGP content,bone calcium,bone phosphorus in model control group rats.Conclusions Gushudan can increases bone density,bone biomechanics,blood BGP content,bone calcium and bone phosphorus induced by prednisolone.These results suggest that Gushudan has a distinct preventive and therapeutic effect on osteoporosis rats caused by administrated prednisolone.
2008年S1期 v.25 114页 [查看摘要][在线阅读][下载 11K] [下载次数：31 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：37 ] Objective To study effects of diabetes mellitus(DM)on pharmacokinetics of cephradine(CED)by comparing the difference in pharmacokinetic behaviours of CED between diabetic and normal rats.Methods DM was induced in male rats by a single iv injection of alloxan 60 mg·kg-1;rats whose blood glucose was over 16 mmol·L-1 were taken as DM group.The rats were divided into DM group and normal control(CTL)group,which were subdivided into low dose(90 mg·kg-1)and high dose(180 mg·kg-1)subgroups.CED was administered by iv or po routes.Blood samples collected at different time post dosing were analyzed by RP-HPLC to yield CED plasma concentration time course.Chromatographic separation was achieved on a Kromasil C18 column(250×4.6 mm ID,5 μm);mobile phase,consisting of 0.025 mol·L-1 KH2PO4-MeOH-CH3CN(87;6∶7 v/v),was delivered at 1.0 mL·min-1;UV detector was set at 261 nm.The peak area ratio of CED to cephalexin(CEX)as internal standard vs concentraion of CED was used to construct calibration curve.50 μL aliquots of TCA-deproteined plasma samples were injected into chromatograph.Results The methodology validation including specificity,precision,accuracy,recovery,limit of quantitation,linearity,stability,etc.,showed that the HPLC assay developed by us completely met requirements of pharmacokinetic study Both DM and CTL groups showed the two-compartment model for iv dosing and extravascular one-compartment model for po dosing as well as first-order kinetics.However,in iv experiment,DM group,when compared with CTL group,presented a significantly shortened t1/2β and MRT as well as increased CL,reflected by t1/2 β 84-91 vs 116-120 min,MRT 61-70 vs 103-119 min;CL 23-25 vs 18-19 mL·min-1·kg-1(P<0.05);in po experiment,a markedly shorter t1/2 K and tmax as well as greater CL and Cmax in DM group than in CTL group were found;meanwhile,DM rats suffered from remarkably increased kidney weight(KW)and KW/BW ratio relative to CTL rats.Conclusions DM pathological status can speed up elimination of CED from body of rats;the compensatory hypertrophy and thereby hyperfunction of kidneys in early-stage diabetics may explain in part at least this accelerated elimanation.
2008年S1期 v.25 114-115页 [查看摘要][在线阅读][下载 21K] [下载次数：46 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：65 ] - 逄蕾;魏敏杰;
目的建立环磷酰胺(CTX)介导的小鼠骨髓抑制动物模型。方法将小鼠随机分为两组即正常对照组(n=8)和CTX组(n=8)。CTX组腹腔注射CTX(120mg·kg-1),一天一次,连续三天,取外周血细胞和骨髓细胞分别计数,并通过流式细胞仪分析骨髓细胞的细胞周期。对照组腹腔注射生理盐水,其他处理同CTX组。结果与正常对照组相比,CTX组WBC和骨髓细胞数分别降至(1.81±0.58)×109.mL-1和2×105.mL-1(P<0.01)。CTX组小鼠骨髓细胞G0/G1期的的比例为(88.57±2.79)%,S期的比例为(7.52±1.59)%,正常对照组分别为(76.61±3.78)%和(18.55±2.99)%,两者有显著差异(P<0.01)。另外,CTX组的骨髓细胞增殖指数(PI)为12.38%,明显低于正常对照组(23.34%)(P<0.01)。结论小鼠骨髓抑制动物模型成功建立。
2008年S1期 v.25 115页 [查看摘要][在线阅读][下载 10K] [下载次数：418 ] |[网刊下载次数：0 ] |[引用频次：3 ] |[阅读次数：91 ] Objective To examine the effect of oral Bordetella pertussis on the asthma mice sensitized by ovalbumin(OVA),and explore the possible mechanism.Methods Culture the B.pertussis in Bordet-Gengou agar containing 25% rabbit blood.Collect the bacteria and inactive them at 80 ℃ for 30 min to get whole killed B.pertussis.32 BALB/C mice were randomly divided into control group,model-control group,model group and treatment group.The mice were sensitized and challenged with OVA to establish asthma model.Asthma mice in treatment group were orally administrated with B.pertussis 7 days before sensitization.The mice in control group and model-control group were challenged with saline.After 24 hours of last challenge,bronchoaveolar lavage fluid(BALF)and peripheral blood were collected.The total cells and eosinophils were counted in BALF.Results Compared with the control group(2.03±0.42,0.33±0.82)×105 mL-1 and model-control group(2.16±0.48,0.16±0.41)×105 mL-1,the total cells(10.13±1.33)×105 mL-1 and eosinophils(11.83±4.573)×105 mL-1 in BALF were more in asthma mice(P<0.01).The number of total cells(5.50±1.55)×105 mL-1 and eosinophils(0.66±0.82)×105 mL-1 in BALF were reduced in asthma mice treated with B.pertussis compared with asthma mice(P<0.01).Conclusions Oral B.pertussis can inhabit airway inflammation of asthma mice and has the potential of treating asthma.
2008年S1期 v.25 115-116页 [查看摘要][在线阅读][下载 23K] [下载次数：36 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：65 ] -
Objective To study the optimum extraction and separation process of total flavonoids in the flowers of Flos Puerariae and its antioxidative activity.Methods The total flavonoids were extracted with assistance of ultrasonic wave and the content was determined at 265 nm wavelength by Spectrophotometric method.Orthogonal experiment L9(34)was carried out to investigate the effects of concentration of solvent,the ratio of material to liquid,time length of extraction,and frequency of extraction on extraction results of total flavonoids from Flos Puerariae.The extracted solution was purified by petroleum ether and ethanol sequently.Under these conditions,the total flavonoids was eluted gradiently with mixed mobile phase of methanol-chloroform solution in the silica gel column system,and then determined by UV scanning and HPLC.Fenton reaction was used to produce and detect hydroxyl radicals(·OH),and pyrogallol system was used to produce and detect the superoxide radical anion(O2-·).Results The optimum conditions were as follows;using 40%(V/V)methanol as extractor with the ratio of material to liquid at 1∶30,and extracting for 2.5 h a time for 3 times.The extraction yield of total flavonoids was 13.6%.Six isoflavone compounds were isolated from the flowers of Flos Puerariae by the method of silica gel column chromatography.Antioxidative test results showed good performance of flavonoid scavenging capacity in both hydroxyl radical system and superoxide radical system and its IC50 was 7.65 μg·mL-1 and 0.18 mg·mL-1,respectively.Conclusions This study provided scientific basis for further development and utilization of Flos Puerariae and make preparation for later pharmacological research.
2008年S1期 v.25 116页 [查看摘要][在线阅读][下载 12K] [下载次数：120 ] |[网刊下载次数：0 ] |[引用频次：1 ] |[阅读次数：38 ] Objective To study the protecting effects and mechanism of betaine hydrochloride on hepatic ischemia-reperfusion injury in rats.Methods Fourty SD rats were randomly divided into 5 groups(8 animals in each group):sham-operated control group(A),hepatic ischemia-reperfusion group(B),200 mg·kg-1 400 mg·kg-1 800 mg·kg-1 betaine hydrochloride+hepatic ischemia-reperfusion group(C、D、E).betaine hydrochloride was administered to animals byoral route in group C、D、E for 7 days before ischemia.A、B group was administered with NS.Made the animal model of part hepatic ischemia-reperfusion.Serum alanine aminotransferase(ALT),aspartate aminotransferase(AST)levels in the blood and themalondialdehyde(MDA),superoxide dismutase(SOD),protein content in hepatic tissue were determined after the liver had been reperfused for 24 hours;the hepatic tissue was examined under lightmicroscope and the cell apoptosis was demonstrated with flow cytometry.Results ALT,AST,MDA increased and SOD decreased significantly in B group when compared those in the A group(P<0.05),Hepatic apoptosis was significantly increased;ALT,AST,MDA decreased and SOD increased significantly in betaine hydrochloride 200 mg·kg-1(C)group when compared those in the B group(P<0.05).Hepatic apoptosis was significantly lower,The histologic changes of the liver tissue under lightmicroscope in the C group was more easer than in the I/R group(B).Conclusions Betaine hydrochloride has the ability to scavenge oxygen free radical(OFR),reduce lipid peroxidation and inhibition of apoptosis.So it can protect the rats liver damaged by ischemia-reperfusion.
2008年S1期 v.25 117-118页 [查看摘要][在线阅读][下载 20K] [下载次数：31 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：55 ] -
Objective The increasing recognition of the role for oxidative stress in hepatic disorders has led to extensive investigation on the protection by exogenous antioxidants against hepatic injury.In this study,we choose two typical polyphenol,quercetin and rutin,to investigate the mechanism of induction of cellular antioxidants and phase 2 enzymes in human HepG2 cells.Methods The HepG2 cells were treated with various concentrations of quercetin and rutin for 6 h and 24 h.The activities of NAD(P)H:quinone oxidoreductase(NQO1)in HepG2 cells were measured by 2,6-dichloroindophenol reduction method.The content of superoxide dismutase(SOD)was determined with the method of chemical colorimetry.The protein expressions of NQO1 and NF-E2-related factor 2(Nrf2)in HepG2 cells were detected by Western blotting.Results Incubation of HepG2 cells with quercetin and rutin resulted in a marked concentration-and time-dependent induction of a number of cellular antioxidants and phase 2 enzymes,including NQO1,SOD.Quercetin and rutin treatment of HepG2 cells also caused increase in protein expressions of NQO1 and Nrf2.Conclusions This study demonstrates that a series of phase 2 enzymes in HepG2 cells can be induced by quercetin and rutin in a concentration-and time-dependent fashion by upregulation the protein expression of nrf2.
2008年S1期 v.25 117页 [查看摘要][在线阅读][下载 10K] [下载次数：53 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：44 ] - 贺素荣;狄安稞;白雪峰;姚维凡;魏敏杰;
目的探讨哮喘模型大鼠肺泡巨噬细胞(alveolar macrophage,AM)电压依赖性钾通道(Voltage-dependent potassiumchannel,KV)活性的变化及其对巨噬细胞功能的影响。方法利用卵蛋白(ovialbumin,OVA)致敏并激发大鼠建立哮喘模型,收集支气管肺泡灌洗液(bronchus alveolarlavagefluid,BALF)培养AM。利用全细胞电压钳模式记录AM细胞膜上的KV电流,观察比较哮喘模型组和对照组KV通道活性的变化。结果哮喘组支气管肺泡灌洗液(BALF)细胞总数显著增高,与对照组(n=7)比较差异显著(P<0.01);哮喘大鼠AM细胞KV电流幅度[(243.56±133.56)pA,n=11]较对照组[(656.23±162.34)pA,n=11]明显降低(P<0.01)。结论哮喘大鼠AM细胞KV通道活性降低,可能导致AM兴奋性增高易被激活分泌各种炎性介质和细胞因子,从而参与哮喘炎症的形成。
2008年S1期 v.25 118页 [查看摘要][在线阅读][下载 10K] [下载次数：40 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：108 ] -
Objective To investigate distribution and excretion of N-Ile1Thr2-63-desulfatohirudin(rH)a recombinant hirudin newly developed in China,in rats for its development as a novel anticoagulant agent.Methods ELISA was used to determine the rH concentration in related tissues and body fluids.Tissues were collected at 15,60 and 180min respectively,after iv administration of rH 1.0 mg·kg-1 to 3 groups of 5 rats,and homogenized.Urine,bile and feces were collected at pre-selected intervals of time after iv dosing 1.0 mg·kg-1 to 3 groups of 5 rats and assayed.Results rH following iv dosing was distributed rapidly,the rH levels in all tissues being found to be the highest at 15 min post-injection,afterwards gradually reduced.The highest concentration of rH was found in blood,the next in lung and heart,the lowest in brain.With 15 min post dose as an example,the rH contents in tissues were ranked in order of plasma>lung>heart >adipose>skeletal muscles>kidney>liver>spleen>brain.The 12 h-cumulative excretion amount of rH in urine and feces accounted for 0.03%and 0.001% of administered dose,respectively;the 6 h-cumulative excretion amount in bile was 0.02%of the dose.Conclusions The rH is distributed mainly in blood circulation system with very low content in other tissues.The drug is excreted from urine,feces and bile of rats in extremely minute amount(only 0.051% dose),suggesting that rH undergoes extensive metabolic elimination in rat body.
2008年S1期 v.25 118-119页 [查看摘要][在线阅读][下载 20K] [下载次数：19 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：38 ] Chinese herbal compound is playing an important role on curing human diseases.And it has been a trend that Chinese herbal compound is being used all over the world in 21 century.However,our Chinese herbal compound is facing serious challenge for the lack of canonical system of quality criterion for Chinese herbal compound so it has been a urgent problem to set up the quality control standards and reveal therapeutic basis of Chinese herbal compound.In order to give full play to the advantages of Chinese herbal compound,modern scientific and technological is used to research of Chinese herbal compound,especially the high performance liquid chromatography tandem mass spectrometry(HPLC-MS),because it is high sensitive,rapid,and obtain more information.It is very necessary that HPLC-MS is uesed to elucidate the effective components of basic substances of Chinese Herbal Compound,and endow traditional Chinese medicine with modern scientific connotation.
2008年S1期 v.25 119页 [查看摘要][在线阅读][下载 10K] [下载次数：102 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：80 ] -
Objective To investigate the antiviral activity of recombinant interferonα-2b suppository(IFNα-2b)in vivo and in vitro.Methods The cytopathic-effect inhibition assay was applied in this study to investigate the antiviral activity of this drug as well as yingtelong and axiluowei as positive control.The guinea pig model of vaginitis and skin infection caused by HSV-2 infection were established,treated with IFNα-2b suppository at dosages of 60000、180000、540000 IU,using IFNα-2b injection 180000 IU·kg-1 as controls.Score the pathological changes of appearance and skin,the virus activities of vaginal secretion and tissue sections of viginae were assayed after treatment.Results The TD50 of IFN α-2b and yingtelong for Vero cells was(>100)μg·mL-1 and(>100000)IU·mL-1,respectively.The IC50 of IFN α-2b and yingtelong and axiluowei for Herpes virus type 1 was(0.29±0.08)μg·mL-1 and(185.0±28.8)IU·mL-1 and(0.19±0.03)μg·mL-1,respectively.The mean scores for vaginal and skin lesion of the treated groups were lower than those of untreated group.Among these concentrations,the IFNα-2b suppository of 540000 IU·kg-1 group.Showed highest anti-viral activity.The virus activity in vaginal secretion of treated group was lower than that of untreated group too(P<0.01 or P<0.05).Tissue sections of viginae after treatment with IFNα-2b suppository showed significantly therapeutical effects on the degrees of vaginal lesion.At the same dosage,The anti-HSV activity of IFNα-2b suppository was also compared with IFNα-2b injection,the results showed that the activity of suppository of 540000 IU·kg-1 group was similar to that of the injection.Conclusions The IFNα-2b suppository has anti-viruses function both in vivo and in vitro.
2008年S1期 v.25 119-120页 [查看摘要][在线阅读][下载 24K] [下载次数：41 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：46 ] Objective Study the β-asaron under the condition that the bowel each segment of rat and be worth in the diffent medicine density and pH of the absorption dynamics characteristic,as to it's the rat absorbs the part in the body and it absorbs the mechanism to carry on the study,for the further design β-asaron settle release the product to provide the living creature medicine learn the basis.Methods Apply the rat to the body to infuse to flow the bowel absorption experiment investigation and absorption dynamics characteristic;adopt the HPLC method measurement β-asaron is in rat body the bowel absorbs the medicine density within the reflux liquid.Results It absorb the quantity and β-asaron of the medicine in the reflux liquid,the density of β-asaron becomes the direct proption,the absorption speed constant of the medicine is basic and constant within the scope of the 19 μg·mL-1-57 μg·mL-1;In the pH is 5.6;6.9;8.0 three kinds of dissimilarities lie the absorption velocity constant of the quality and absorb the of percentage and also did not show the difference of salience;β-asaron is in the small intestines the lower part absorb better,absorbthe velocity to press to return to bowel,ileum,jejunum,duodenum,colon to descend one by one in order,absorb the velocity constant one by one in order is 0.402,0.396,0.385,0.325 h-1.Conclusions β-asaron absorbs to present a class absorption dynamics characteristic in the bowel way,absorbing the mechanism as passive absorption;in order to return to ileum and jejunums,main absorption part there is certain absorption in the colon,too.
2008年S1期 v.25 120页 [查看摘要][在线阅读][下载 14K] [下载次数：14 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：35 ] -
The sex-based differences between the effects of two novel sugar-based drug candidates,a sulfated polymannuroguluronate(SPMG-911)and an acidic oligosaccharide sugar chain compound(AOSC-971),on the enzymes CYP 1A2,CYP2E1 and CYP3A4 of Chinese human liver microsome were investigated.The results showed that neither SPMG-911 nor AOSC-971 have any effect on CYP3A4,AOSC-971 induced the CYP 2E1 in men but have no effect on CYP1A2,SPMG-911 inhibit the CYP1A2 also in men but have no effect on CYP2E1.The results are useful for their safety evaluation,as well as for the prediction of inter-drug interactions associated with the two drugs.
2008年S1期 v.25 121-122页 [查看摘要][在线阅读][下载 16K] [下载次数：55 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：80 ] - 陈磊;聂宏光;李金鸣;金万宝;
目的研究早期糖尿病大鼠背根神经节(DRG)以及主动脉中COX-2mRNA及血中PGE2的变化,探讨COX-2mRNA和血中PGE2之间的关系。方法单次注射链佐霉素60mg·kg-1制作大鼠糖尿病模型,随机分成5组:分别为糖尿病模型组1W,3W,4W,8W和对照组。用RT-PCR技术半定量测定DRG中COX-2mRNA,用放射免疫法检测血浆PGE2的浓度。结果DRG中COX-2mRNA与血浆PGE2的变化趋势相同:1W开始增加,3W达峰值,患病后4W内降至基础水平。对照组血浆PGE2未检出,模型组1W增加至453.3±172.8pg·mL-1,3W达到峰值2500±592.14pg.mL-1,到4W时降至380±112.3pg·mL-1,8W后又增至740±173.2pg·mL-1。DRG中COX-2mRNA1W开始上升,3W达到峰值,4W内降至基础水平。主动脉中COX-2mRNA:对照组最高,1W开始下降,8W恢复至正常水平。结论糖尿病大鼠早期血浆PGE2浓度可能部分受DRG中COX-2mRNA水平的调节。
2008年S1期 v.25 121页 [查看摘要][在线阅读][下载 6K] [下载次数：73 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：93 ] - 温晓艳;吴慧哲;逄蕾;刘明妍;金万宝;魏敏杰;
目的建立一种灵敏,简便,快速测定人体血浆中尼莫地平血药浓度的HPLC方法。方法色谱柱:美国WatersSymmetry C18柱(5μm150mm×4.6mm);流动相:甲醇∶水∶三乙胺(65∶35∶0.02v/v/v);流速:1.0mL·min-1;检测波长:358nm,尼莫地平碱化后经正己烷/乙醚(1∶1v/v)提取后测试。结果尼莫地平在1.25～80μg.L-1范围内线性良好,尼莫地平与内标面积比为纵坐标进行线性回归,得回归方程为:y=0.0477x+0.0233,r2=0.9997,最低检测浓度为:1.25μg.L-1,方法回收率为:(96.44±8.49)%,(n=5),日内日间精密度为6.62%和10.90%;结论该方法适于人体血浆内尼莫地平的检测并可应用于药动学研究。
2008年S1期 v.25 121页 [查看摘要][在线阅读][下载 6K] [下载次数：93 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：121 ] Objective To investigate the effects of TGF-β on the expressions and distribution of phosphorated Smad2/3 and Smad7 in hepatic stem-like cells.Methods Using immunogold transmission electron microscopy,we observed the expressions and distribution of phosphorated Smad2/3,and Smad7 before and after TGF-β1(5 ng·mL-1)treatment for 4,8,and 24 hours in hepatic stem-like cells(WB cells).In addition,we also detected the apoptosis status after TGF-β1 stimulation by transmission electron microscopy.Results TGF-β1 stimulation can result in expression increasing of phosphorated Smad2/3 in WB cells,and reach the peak at 8 h,especially in the nuclear.After treatment with TGF-β1 for 24 h,the nuclear expression of phosphorated Smad2/3 gradually decreased.Additionally,we found that TGF-β1 treatment also contributed to increasing in protein level and alteration in cellular distribution of Smad7(translocation from the nucleus to the cytoplasm)in WB cells.Furthermore,we observed apoptotic body in WB cells after TGF-β1 treatment for 8 h.Conclusions These results indicate that TGF-β stimulation can alter the expression and cellular distribution of phosphorated Smad2/3 and Smad7 which are its downstream molecular,suggesting hepatic stem-like cells own intact responding to TGF-β.
2008年S1期 v.25 122页 [查看摘要][在线阅读][下载 10K] [下载次数：29 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：49 ] -
Objective To investigate the spasmolytic and anti-diarrheal activities of 3,4-dihydro-2-(4-morpholinylmethy)-1(2H)-naphthalenone(CY),which was first synthesized by Welch,Willard M et al.in 1977.Methods The spasmolytic effects of CY were tested on isolated rabbit small intestine at the concentration of 0.01 to 3 mM;the diarrheal-index was evaluated on diarrhea mice to study the anti-diarrheal activities of CY.Results CY(0.1-1 mM)inhibited spontaneous motility of rabbit small intestine and at the concentration of 0.01 to 3 mM CY inhibited the contractile response of rabbit small intestine and colon induced by acetylcholine(10-2 mg·mL-1),high K+(60 mM)and BaCl2(1 mg·mL-1).When tested against calcium channel blocked in rabbit small intestine and colon,CY caused a rightward shift in the Ca2+ dose-response curves,similar to that produced by verapamil,a well-known calcium antagonist.CY could inhibit the diarrhea induced by castor oil,MgSO4 and liquid paraffin and LD50 of CY is 277.2 mg·kg-1.Conclusions CY may produce its spasmolytic and anti-diarrheal effects as a calcium antagonist.
2008年S1期 v.25 122-123页 [查看摘要][在线阅读][下载 23K] [下载次数：23 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：44 ] Objective To investigate the relationship between the consumption of antibacterial agents and resistance rate of Klebsiela pneumoniae(KP)in the hospital respiratory unit for 3 consecutive years in 2005-2007.Methods The total antibacterial consumption expressed as defined DDDs/100BD,as well as resistance rate of total KP and producing ESBLs KP were collected,and their correlation was analyzed.Results The rate of resistance of KP to cefoperazone/sulbactam,Cefepime,Imipenem,Moxifloxacin was significantly positively associated with the consumption of Cefotaxime,Ceftazidime,Moxifloxacin,Amikacin respectively;A significant positive association was observed between the rate of resistance of KP to Piperacillin/Tazobactam,Ceftriaxone and the consumption of Imipenem;The rate of resistance of KP to Piperacillin,Cefotaxime,Ciprofloxacin was significantly positively associated with the consumption of Levofloxacin.ESBLs producing bacilli of KP were detected in 44 of 75 isolates(58.7%),The rate of resistance of producing ESBLs KP to Piperacillin/Tazobactam,Ceftriaxone was significantly positively associated with the consumption of Imipenem,Ceftazidime;A significant positive association was observed between the rate of resistance of producing ESBLs KP to Piperacillin,Imipenem and the consumption of Moxifloxacin.There was no significant correlation in other drugs.Conclusions A relationship existed between antimicrobial consumption and rates of resistance of KP in the hospital respiratory unit.We must use antibiotics carefully and with reason to control and lessen the drug resistance of bacterial.
2008年S1期 v.25 123页 [查看摘要][在线阅读][下载 12K] [下载次数：18 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：37 ] -
Objective The standard extract of Pueraria Lobata(SEP)was extracted from the traditional Chinese medicine Pueraria Lobata.and the anti-osteoporotic effect of SEP were evaluated in the paper.Methods The ovariotomied rats were used simulating osteoporosis model,and characterized from thighbone measurement,bone density,blood biochemistry assay,emiction biochemistry,bone morphology and womb pathology were also determined.Results The ovariotomy causes rats' weight,serum ALP,Strap,bone calcium element,emiction calcium element,emiction hydroxide praline increased;bone calcium content,bone density and rigidity,thighbone wet weight,dry weight and ash weight remarkably reduced;and the bone anti-bend intensity,the maximum bend strength decreased,the bone girder thinner,or even be broken.This indicates that ovariotomy causes rats lost bone calcium and got osteoporosis.One month after operation,SEP was provided subsequently for 12 weeks to different samples(medicament quantity 2.5,1.25,0.625 g·kg-1;model group;fake operational group and masculine medicament estrogen group).It was found that SEP can suppress the weight increase caused by ovariotomy,improved the thighbone metrology standard of the OVX rats(the bone calcium content 26.2%,20.1% and 15.7% separately);increase the thighbone density and rigidity,the thighbone wet weight,dry weight and ash weight;increased blood calcium,blood phosphorus,decreasing ALP,Strap,increasing serum estradiol level,reducing bone calcium content;improve the emiction biochemistry characteristics:decreased emiction calcium,emiction hydroxide proline ejection amount;improved the OVX rats thighbone biomechanics characteristic:increased the anti-band intensity and maximum bend strength.Conclusions SEP exerted upon an inhibited effects on osteoporosis caused by ovariotomy.
2008年S1期 v.25 124页 [查看摘要][在线阅读][下载 11K] [下载次数：44 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：39 ] Objective To search the effects of Bixieqianggupian(BXQBP)on osteoporosis.Methods The experimental models of osteoporosis(OP)induced by ovariectomy(OVX),retinoic acid(RA)and dexamethasone(DXM)in rats were introduced in this study.In the same time,the influence on tibia fracture healing in rats was also observed.Moreover,the anti-inflammation effects and analgesia of BXQBP in mice and rats were also studied.Results The body weight gain induced by OVX was prevented obviously by administering BXQBP.And serum estradiol and bone gla protein(BGP)were examined by RIA,and results showed that estradiol increased and BGP decreased.Bone mineral density(BMD),bone mineral content(BMC)and bone mass of femur had increased,moreover,calcium content of bone(monitored by atomic absorption)had been improved significantly after BXQBP administration.Furthermore,biomechanical characters of bone were measured by three point bending test,and the anti-bend intensity and maximum bend strength increased remarkably.The alkaline phosphatese(ALP)decreased.And amount of urine calcium(Ca)and hydroxyproline(HOP)decreased obviously.However,effect on the proliferation of endometria was not obvious.The RA induced OP model.Compared with model,the BMD and BMC increased markedly in BXQBP rats(i.g.30 days).And bone mass and calcium content were increased.Then BGP and ALP decreased by administering BXQBP.The anti-band intensity and maximum bend strength increased evidently.And ejection of urine Ca and HOP decreased obviously.The bone trabecula became thinner,and arranged in disorder in OP rats,however,the status was reversed obviously by administrating BXQBP.The OP model also induced by DXM in rats:Effect against weight losing caused by DXM was observed in groups of three doses(i.g.12 weeks)of BXQBP.And BMD,BMC,bone mass and calcium content increased evidently.The results showed that the fracture healing had been enhanced obviously at three doses(i.g.40 days),callus growth was promoted and bone rigidity was reinforced.Moreover,BXQBP had the anti-inflammation and analgesia effects in mice and rats.Conclusions These results indicated that BXQBP had an obviously protective effect on osteoporosis in experimental animals,and promoted the fracture healing.
2008年S1期 v.25 124-125页 [查看摘要][在线阅读][下载 24K] [下载次数：19 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：35 ] -
Objective To evaluate the effect of Ginsenoside Re on Shock through different animal models in order to provide preclinical pharmacological experimental data.Methods In superior mesenteric artery occlusion(SMAO)of rats model was established by clamping superior mesenteric artery(SMA)for 2 hours and then reperfusing for another 2 hours.During the whole process mean artery pressure(MAP)and heart rate(HR)were recorded.The blood samples were collected before and 2 hours after clamping respectively,to determine serum GOT,GPT,LDH,GLU,CK,BUN,Cr and NO.Intestine,lung,heart,kidney and liver tissue samples were also collected after reperfusion 2 hours,and(1)protein concentration of bronchia alveolus lung fluid [BALF],(2)HSP70 expression in heart and kidney(3)histology pathology and(4)oxidation injury(MDA and GSH-Px)in above tissues were determined.Hemorrhagic shock(HS)of cats,scald shock model and insulin shock model were also introduced here.Results Ginsenoside Re decreased the morality of SMAO rats and the GOT,GPT,LDH,CK,BUN,NO and Cr level,the GSH-Px activity was increased and MDA content was decreased.The expression of HSP70 in heart and kidney were up-regulated and the protein content in BALF was inhibited after Ginsenoside Re treatment.Ginsenoside Re corrected acidosis induced by HS,and elevated Hb content,reduced serum MDA,LD level.Ginsenoside Re could attenuate liver and lung tissue injury.In scald shock,Ginsenoside Re decreased LDH,CK-MB,a-HBD and Hct of serum and in insulin shock survival time was prolonged.Conclusions Ginsenoside Re showed an anti-shock activity.
2008年S1期 v.25 125页 [查看摘要][在线阅读][下载 12K] [下载次数：39 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：24 ] Objective To further authenticate the role of melatonin on endogenous biologic clock system.Methods Pinealectomized mice were used in the experiments,a series of circadian rhythm of physiology index,such as glucocorticoid,amino acid neurotransmitter,immune function,sensitivity of algesia and body temperature were measured.Results Effects of melatonin on endogenous circadian rhythm roughly appeared four forms:1)The model of inherent rhythm was invariant,but midvalue was removed.2)Pacing function:pinealectomy and melatonin administration changed amplitude of the circadian vibration of aspartate,peripheral blood WBC and serum hemolysin.3)Phase of rhythm changed,such as the effects on percentage of lymphocyte and sensitivity of algesia.4)No effect,the circadian rhythm of body temperature belong to this form.Conclusions Melatonin has effects some circadian rhythm,and it can adjust endogenous inherent rhythm and make the rhythm keep step with environmental cycle.Melatonin may be a kind of Zeitgeber,Pineal gland might being a rhythm bearing organ to some circadian rhythm.
2008年S1期 v.25 126-127页 [查看摘要][在线阅读][下载 23K] [下载次数：25 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：31 ] -
Objective Searching the function that the Injection of the matrine hydrochloride prevents and cures acute chemical liver injury of mice、immunity liver injury of mice and chronic liver injury of rats.Methods Acute hepatic injury models of mice induced by Chemical poison carbon tetrachloride(CCl4),thioacetamide(TAA),D-galactosamine(D-GalN),immunity hepatic injury model of mice induced by BCG and fat polysaccharide(LPS),chronic liver injury model of rats induced by CCl4 were introduced in the experiment.The serum ALT and AST were measured in acute hepatic injury experiments.Serum ALT,AST,AKP,ALB,TP,BiL-T,creatinine,triglyceride,sialic acid,laminin,hyaluronic acid,type Ⅲ procollagen and type Ⅳ collagen,hepatic hydroxyproline(HyP)of rats in chronic liver injury animals were determined after Injection of the matrine hydrochloride.Results The Injection of the matrine hydrochloride reduced serum ALT and AST level of acute chemical liver injury of mice induced by CCl4,TAA and D-GalN.The index of the liver and the spleen of immunity liver injury of mice induced by BCG and LPS were decreased after the injection of matrine hydrochloride treatment.Compared with the model group,the injection may obviously inhibited serum ALT,AST,TP,AKP,TRI,BiL-T,creatinine,triglyceride,sialic acid,laminin,hyaluronic acid,type Ⅲ procollagen and type Ⅳ collagen activity of chronic liver injury of rats induced by CCl4,elevated ALB、A/G,reduced the liver HyP,decreased the index of the liver and the spleen.The liver visual observation,the pathology inspection and the HAI grading result showed the injection may reduce the inflammatory activity in liver tissue,restrain the liver cell damage,reduce the pseudolobuli formation.Conclusions The Injection of matrine hydrochloride had the protective function to acute chemical hepatic injury of mice induced by CCl4、TAA、D-GalN、immunity hepatic injury of mice induced by the BCG and LPS and chronic liver injury of rats induced by CCl4.
2008年S1期 v.25 126页 [查看摘要][在线阅读][下载 12K] [下载次数：34 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：69 ] Objective To search the effects of the extractive E of Ginseng(EG)on experimental climacteric syndrome in rats.Methods Extirpating the both sides of ovary of rats to turbulence estrogen secretion,induce climacteric syndrome.The weight,bite and sup,substance of bone,blood lipid,calcium urine biochemistry,estrodiol,behavior perfomance were also observed.Results The body weight of ovariotomied rat was controlled,bone density was increased,estradiol level increased,the weight of bone increased.Conclusions EG ameliorated climacteric syndrome.Increase bone density and bone mine content,enhanced the level of estradiol.
2008年S1期 v.25 127页 [查看摘要][在线阅读][下载 11K] [下载次数：25 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：77 ] -
Objective The present in vivo study was undertaken to determine whether matrine,a kind of traditional Chinese medicinal alkaloid,would relax the isolated guinea pig aortic smooth muscles,if so,to investigate the mechanism involved.Methods The concentration-dependent relaxation response to matrine was studied in phenylephrine or potassium chloride precontracted guinea pig aortic rings.Results Matrine(1×10-4 M-3.3×10-3 M)relaxed the endothelium denuded aortic rings precontracted submaximally with phenylephrine,in a concentration-dependent manner,and it's preincubation(3.3×10-3 M)produced a significant rightward shift in the phenylephrine dose-response curve,but had no effects on the potassium chloride-induced contraction.The anticontractile effect of matrine was not reduced by the highly selective ATP-dependent K+ channel blocker glibenclamide(10-5 M),the non-selective K+ channel blocker tetraethylammonium(10-3 M),as well as the β-antagonist propranolol(10-5 M).In either "normal" or "Ca2+-free" bathing medium,the phenylephrine-induced contraction was attenuated by matrine(3.3×10-3 M),indicating the vasorelaxation was due to inhibit of intracellular and extracellular Ca2+ mobilization.Conclusions The results obtained clearly demonstrated that matrine inhibits phenylephrine-induced contractions by inhibiting activation of α-adrenoceptor and interfering with both the release of intracellular Ca2+ and the influx of extracellular Ca2+.
2008年S1期 v.25 127-128页 [查看摘要][在线阅读][下载 21K] [下载次数：23 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：41 ] Objective Pesticides has gain an increasing awareness because of it is becoming a serious environmental problem and come to threaten the health of humanbeing.The effect of five pesticides(zineb,copforce,the mixture of carbendazim and mancozeb,hymexazol)on soil bacteria,fungi,actinomyces,and Five specific enzymes were chosen for investigation(urease,dehydrogenase,invertase,acid phosphates and protease).Methods The enumeration of the soil micro flora was done by the dilution plate method;The enzyme activity was determined by traditional methods.Shannon-Wiener index as well as 16S rRNA-PCR amplification and DGGE fingerprinting was used for detection of shift in microbial community diversity in pesticides contaminated agricultural soil.Results The outcome showed that the microbial diversity was significantly changed after the application of pesticides,the effect of pesticides on microbe had a order from top to bottom:bacteria-actinomyces-fungi.Conclusions Our results indicate that the use of the pesticides hymexazol resulted in an altered soil community structure,in particular for the actinomyces.Invertase was markedly inhibited by hymexazol,zineb,carbendazim and mancozeb and the inhibiting rates were varied between 30.30% and 21.21%;Urease activity was also inhibited significantly by hymexazol,the inhibiting rate was 37.67%;Protease activity was markedly inhibited by zineb and hymexazol,the inhibiting rates were 27.27% and 18.18% respectively;Phosphates activity was inhibited significantly by hymexazol,zineb,carbendazim and mancozeb,the inhibiting rates were range from 22.12%-3.54%;Dehydrogenase activity was not significantly affected by pesticides.Meanwhile,the correlation of all indexes were analyzed,the data suggested that all indexes existed certain correlation.
2008年S1期 v.25 128页 [查看摘要][在线阅读][下载 10K] [下载次数：95 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：48 ] -
Objective To clone the ACP(acyl carrier protein)gene in Jatropha curcas L.,a potential anti-tumour and anti-fungal plant.And to determinate the expression of ACP in Jatropha curcas L.Methods A cDNA clone encoding ACP(acyl carrier protein)was isolated from Jatropha curcas L.endosperm cDNA library by random sequencing.The expression of ACP gene was investigated by semi-quantitative RT-PCR in leaves,stems and seeds of J.curca.The expression of ACP was also investigated in germinating seeds.The fragment encoding ACP protein in J.curca.was inserted into a prokaryotic expression vector pET28a(+).The gene was overexpressed in E.coli BL21 to produce abundant protein.Immunohistochemical analysis was used to detect the expression of ACP in different tissues of J.curca.Results The cDNA sequence was 806 bp in length and the ORF was 393 bp.The predicted molecular weight of the putative protein was 14.4 kD,pI=5.2.It contained a 4'-phosphopantetheine-binding motif.This prosthetic group can be combined with Serine of ACP protein.Semi-quantitative RT-PCR analysis showed that ACP gene was expressed in leaves,stems and seeds of J.curcas.The expression level of ACP was the highest in seeds and it was not detected in roots.After seeds germinated,the expression level of ACP in seeds increased progressively and reached a peak at 96 h.After induced by IPTG,SDS-PAGE analysis showed that the ACP protein of 20 kD was expressed.Immunohistochemical analysis showed that ACP specifical expressed abundantly in embyo of the seeds,and it was not detected in roots and the emdosperm while expressed in leaves and stems.Conclusions A cDNA clone encoding ACP which had all the typical characteristics of ACPs was isolated.It was expressed successfully in E.coli.The results of semi-quantitative RT-PCR analysis and immunohistochemical analysis were very similar,which showed that the expression of ACP in J.curcas.was abundant in seeds.The results indicated the expression related to the high metabolism.
2008年S1期 v.25 128-129页 [查看摘要][在线阅读][下载 24K] [下载次数：38 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：45 ] Objective To enhance the solubility,quicken the speed of digesting and absorption,and increase the bioavailability of quercetin(3,3',4',5,7-pentahydroxyflavone).Methods A series of Quercetin-PEG4000 solid dispersions were prepared by fusion method.The configuration and property of solid dispersion were characterized by solubility tests,dissolution tests,FTIR spectra,differential scanning calorimetry(DSC)and microphotograph.Results 1.According to solubility tests the the mass ratio of quercetin to PEG4000 affected strongly on the solubility of solid dispersions,on the whole,the relation of the solubility of solid dispersions to the mass ratio presented linear relationship.The preparation temperature had little effect on the solubility of solid dispersions.The surface-active agent,polysorbate80 increased strongly the solubility of solid dispersions.2.According to the dissolution tests,the mass ratio of quercetin to PEG4000 affected strongly on the dissolution of solid dispersions,the preparation temperature had little effect on the dissolution of solid dispersions.The surface-active agent,polysorbate80 increased strongly the dissolution of solid dispersions,and after addition polysorbate80,the dissolution of solid dispersions was two times of the dissolution of solid dispersions without polysorbate80.3.According to the DSC results,except that a little of quercetin molecular existed as crystalline state in the solid dispersion with the mass ratio was qu:PEG=1:2,quercetin existed as amorphous phase in other mass ratio solid dispersion.4.According to the FTIR spectra and microphotograph results,the relation of quercetin and PEG4000 was mainly physical mixing in quercetin-PEG4000 solid dispersion.Quercetin was just like solute in solution,and PEG4000 was just like solvent in solution.The force between quercetin and PEG4000 was mainly hydrogen bonding,so the biological activity of quercetin would not be influenced greatly after the formation solid dispersion.Conclusions These results suggest that quercetin existed mainly as amorphous phase in solid dispersion;the solubility and the dissolution in water were increased obviously after formation the solid dispersion.
2008年S1期 v.25 129-130页 [查看摘要][在线阅读][下载 26K] [下载次数：98 ] |[网刊下载次数：0 ] |[引用频次：1 ] |[阅读次数：44 ] -
Objective To study the effects of melatonin on pethidine-induced physical dependence and its antioxidative action.Methods A trauma-pain model was established in Wistar rats by combining right limb amputation with 50 ℃ tail-flick test.The contents of MDA and the activity of the total superoxide dismutase(SOD)in the brain tissue of trauma-pain rats were detected by thiobarbituric acid method and the xanthine oxidase method.A physical dependence model in mice was reproduced by subcutaneous injection of pethidine and the withdrawal syndromes were induced by intraperitoneal injection of naloxone.Results The contents of MDA enhanced,but the activity of SOD decreased greatly in brain tissues postinjury in rats.Melatonin(30,60,120 mg·kg-1)i.p.reduced the contents of MDA and enhanced the activity of SOD dose-dependently.Melatonin alone showed no withdrawal syndrome when it was given until the dosage of 840 mg·kg-1.Moreover,Melatonin(5,15,20 mg·kg-1)obviously inhibited the withdrawal jumpings of mice in pethidine-treated groups dose-dependently(P<0.01),the jumping rates of mice were decreased 61.4%,72.8%,84.8%,respectively.Conclusions The present results indicated that melatonin has good antioxidative effects on the trauma rats.In addiction,melatonin might inhibit withdrawal syndromes in pethidine-dependent mice.
2008年S1期 v.25 130页 [查看摘要][在线阅读][下载 12K] [下载次数：11 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：80 ] Objective To analyse the potential involvement of the opioid receptor gene expression in the mechanisms of the analgesic action of melatonin.Methods A trauma-pain model was established in Wistar rats by combining right-hind limb amputation with 50 ℃ tail-flick test.Antinociception was determined by tail-flick latency to hot waster at 50 ℃.RT-PCR was used to observe the the expression of the M1OR and KOR gene.Results Melatonin produced the antinociceptive effect in dose-dependent manner after i.p or i.c.v.administration.Injected i.c.v.to rats,naloxone(10 μg)obviously antagonized the antinociceptive effect induced by i.p.melatonin.The expression of the M1OR gene in the rat hypothalamus and the KOR gene in the hippocampus was both significantly reduced at day 3 after injury,which was parallel to the reduction of the rat pain thresholds.However,the expression of the M1OR gene in the hippocampus and the KOR gene in the hypothalamus was not changed.Treatment of trauma-pain rats with melatonin(30-120 mg·kg-1)i.p.administrated induced the up-regulation of M1OR mRNA in the hypothalamus and the KOR mRNA in the hippocampus in a concentration-dependent manner.Conclusions The present observations suggest that Melatonin-induced antinociceptive effect may partially contribute to the up-regulation of M1OR mRNA level in the hypothalamus and the KOR mRNA level in the hippocampus.
2008年S1期 v.25 130-131页 [查看摘要][在线阅读][下载 24K] [下载次数：19 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：43 ] -
Objective The purpose of the study is to investigate the effects of Charred Fructus Crataegi Alcohol Extract on contractililty of isolated rat gastric and intesting smooth muscle strips.Methods Isolated rat intestine was selected in the assay to test the effects of Charred Fructus Crataegi Alcohol Extract on contractilty of isolated rat gastric and intestine smooth muscle strips using Krebs' solution,to observe the effects of in the presence of acetylcholine or atropine.Results Charred Fructus Crataegi Alcohol Extract in the range of 2-8 mg crude drugs/mL could significantly reduce the contractility of rat gastric and intestine smooth muscle strips in a dose-dependent manner,and Charred Fructus Crataegi Alcohol Extract 8 mg·mL-1(crude drugs)could inhibit the stimulation induced by acetylcholine.Charred Fructus Crataegi Alcohol Extract 8 mg·mL-1(crude drugs)was found to have a inhibiton of the relaxtion concurrently used with atropin.Conclusions The results suggest that Charred Fructus Crataegi Alcohol Extract has prominent inhibitory effects on the contractile activity of isolated rat gastric and intestine smooth muscle strips.
2008年S1期 v.25 131页 [查看摘要][在线阅读][下载 11K] [下载次数：24 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：58 ] - 王芳;杨静玉;李经才;吴春福;
目的研究两种内源性睡眠促进物质褪黑素和油酰胺联合应用后对大鼠催眠作用的变化。方法大鼠腹腔注射褪黑素(2.5,10mg·kg-1),油酰胺(25,50mg·kg-1)或联合应用褪黑素(2.5,10mg·kg-1)与油酰胺(25,50mg·kg-1)后,立即记录大鼠脑电和肌电变化。结果虽然褪黑素(2.5mg·kg-1)和油酰胺(25mg·kg-1)单独应用没有对大鼠脑电图产生明显影响,联合应用后显著缩短睡眠潜伏期(TSO)和觉醒时间(W),并且延长了慢波睡眠(SWS)和总睡眠时间(TS)。褪黑素(10mg·kg-1)和油酰胺(50mg·kg-1)单独具有明显的催眠作用,但联合应用后快波睡眠(PS)减少,其它睡眠指标未见变化。结论褪黑素和油酰胺联合应用后对大鼠催眠作用的变化较为复杂,其机制应进一步深入研究。
2008年S1期 v.25 132页 [查看摘要][在线阅读][下载 6K] [下载次数：145 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：140 ] - 姜峰;王芳;杨静玉;宋彦卓;吴春福;
目的优化红景天(R)和冬虫夏草(C)联合应用的抗缺氧的最佳剂量配比,同时对抗缺氧性应激的作用机制进行了初步探讨。方法采用两因素三水平正交设计方法,筛选出两者联合应用的最佳剂量配比,并对该组方(RC)的抗缺氧性应激作用及初步机制进行了研究。结果经正交设计筛选出的RC组方在最佳剂量配比下,能显著延长正常小鼠常压耐缺氧时间,效果显著优于单方,并具有时间依赖性。同时RC能显著延长亚硝酸钠中毒小鼠存活时间和急性脑缺血性缺氧后小鼠呼吸次数。并且RC能显著增加缺氧小鼠血液中Hb的含量和RBC数量,能明显降低小鼠缺氧后心、脑组织中的MDA含量,增加小鼠缺氧后心、脑组织中SOD活性,并且对小鼠缺氧后脑组织中GSH含量的降低也有改善作用,除此之外,RC还能显著减少小鼠缺氧后血液中LD的含量并同时增加血液中LDH活性。结论红景天与冬虫夏草组方后药效显著优于单方。对缺氧性应激产生的损伤具有明显的保护作用。其抗缺氧性应激损伤的机制可能与提高缺氧小鼠血液的载氧能力和增强抗氧化系统活性有关。
2008年S1期 v.25 132页 [查看摘要][在线阅读][下载 6K] [下载次数：110 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：105 ] - 李玉珠;王芳;王立辉;杨静玉;吴春福;
目的本文研究了海星醇提取物HX对肾上腺素、西沙必利所致胃肠运动异常的双向调节作用,同时初步探讨了HX拮抗肾上腺素所致胃肠动力抑制的机制。方法采用家兔离体肠管张力测定、小鼠胃排空及小肠推进实验测定HX对胃肠动力的调节作用。采用放免法测定胃泌素和胃动素水平。结果HX可显著拮抗肾上腺素所致家兔离体肠管张力的降低。连续6天灌胃给予HX(1.3g·kg-1)对肾上腺素所致小鼠胃排空抑制具有显著的拮抗作用,HX(1.3,2.6g.kg-1)对肾上腺素所致小肠推进的抑制具有显著的拮抗作用。除此之外,研究发现连续6天灌胃给予HX(1.3g·kg-1)对西沙必利引起的小鼠胃排空亢进具有拮抗作用,HX(1.3,3.9g·kg-1)可抑制西沙必利模型组小鼠小肠推进。进一步研究发现HX各剂量对肾上腺素引起的大鼠血液中胃泌素和胃动素水平的降低有升高趋势,但没有统计学差异。结论HX对小鼠胃肠动力具有一定程度的双向调节作用,其作用可能与肾上腺素受体和5-HT受体有关。
2008年S1期 v.25 132-133页 [查看摘要][在线阅读][下载 11K] [下载次数：157 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：84 ] - 金鑫鑫;耿芳;谭丽丽;杨柯;王立辉;杨静玉;
目的探讨纯镁及镁合金材料作为骨组织工程支架材料的可行性。方法通过细胞毒性试验、遗传毒性实验、急性全身毒性试验、血液相容性试验评价材料的安全性。用直接接触的方法,通过AO/EB染色、扫描电镜、ALP活性测定考察材料的生物相容性。结果1%、10%、50%、100%镁及镁合金涂层材料浸提液作用MG63细胞24小时,细胞存活率均大于80%,细胞周期无改变,DNA无损伤。小鼠腹腔注射100%材料浸提液,72小时内无死亡,并且体重与空白对照组比无显著差异。100%纯镁材料浸提液和镁合金材料浸提液的溶血率分别为0.58%和0.33%。细胞复合材料,AO/EB染色观察到细胞在材料表面大量存活,形态正常。扫描电镜结果显示细胞种植于材料表面7天后,可以在材料表面伸展良好,分泌大量的细胞外基质,且ALP活性良好。结论纯镁材料和镁合金材料无细胞毒性和遗传毒性,无急性全身毒性,而不产生溶血现象。与细胞复合后,具有良好的生物相容性。
2008年S1期 v.25 133页 [查看摘要][在线阅读][下载 5K] [下载次数：337 ] |[网刊下载次数：0 ] |[引用频次：5 ] |[阅读次数：146 ] - 冯婉玉;顾玲玲;李霄理;
目的建立一种人血浆中卵磷脂络合碘浓度测定方法。方法采用衍生气相色谱法,在酸性环境下将其衍生成碘丁酮,环己烷萃取后1μL进样分析。采用毛细管色谱柱OV-1701(50m×0.53mm),电子捕获检测器。气化室温度:230℃,柱温:105℃;检测器温度:260℃,高纯氮气10mL·min-1。结果血浆中药物浓度在0.04～0.4μg·mL-1内线性关系良好(r=0.9954),最低检测限为0.02μg·mL-1,平均回收率82.55%,RSD为2.864%。结论该方法结果准确,可靠,使用于测定人血浆中卵磷脂络合碘浓度。
2008年S1期 v.25 133页 [查看摘要][在线阅读][下载 5K] [下载次数：123 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：129 ] - 鞠学鹏;孙明立;赵海山;姚维凡;魏敏杰;
目的应用膏状固体酒精灼烧法建立一种新的深度及面积均可控的大鼠烧伤模型。方法Wistar清洁级健康大白鼠30只,于造模前一日以8%Na2S酒精溶液脱毛。造模时,将膏状固体酒精均匀涂抹于预烧伤区,涂抹面积与预烧伤面积一致,立即点燃并计时,烧伤时间分别为5、15、30、45、60秒。造模24小时后取烧伤皮肤组织做病理形态学检查。结果烧伤深度与烧伤时间呈正相关,浅二度烧伤、深二度烧伤、三度烧伤所需烧伤时间分别为15、30、45秒。烧伤皮肤与正常皮肤分界清晰,烧伤面积与涂抹膏状固体酒精的面积基本一致。结论在本模型中烧伤深度及烧伤面积均可得到很好的控制,通过简单的调整即可获得不同级别的烧伤模型。
2008年S1期 v.25 133-134页 [查看摘要][在线阅读][下载 11K] [下载次数：387 ] |[网刊下载次数：0 ] |[引用频次：4 ] |[阅读次数：114 ] - 李春莉;杨宝峰;张景海;焦军东;单宏丽;吴春福;
目的研究重组蝎抗神经兴奋肽(ANEPⅢ)对培养大鼠海马神经元钠电流以及通道动力学的影响。方法采用全细胞膜片钳记录模式考察海马神经元钠通道电流的变化。结果ANEPⅢ可显著降低海马神经元钠电流,并呈剂量依赖性,半数抑制浓度为214.76nM。离子通道动力学研究表明ANEPⅢ对海马神经元钠电流的稳态失活无明显影响,可使钠电流的恢复减慢。结论重组蝎毒抗神经兴奋肽ANEPⅢ可抑制培养大鼠海马神经元钠电流,使其复活过程减慢,这可能与其发挥功能活性密切相关。
2008年S1期 v.25 134页 [查看摘要][在线阅读][下载 5K] [下载次数：157 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：164 ] - 牟艳华;杨静玉;张弘;吴春福;
目的以往体内实验研究表明,乙醇能够引起纹状体、伏隔核和大脑皮层等部位抗坏血酸(AA)的释放,一些药物参与调节乙醇引起的AA的释放。此文要验证原花青素对神经元的直接作用,为乙醇损伤的脑保护治疗提供理论依据。方法原代培养大鼠皮层神经元与AA孵育1～3h后洗去,单独给予乙醇或药物和乙醇共同作用30min,收集细胞外液处理后以HPLC-EC检测抗坏血酸和脱氢抗坏血酸含量。结果原花青素能够抑制乙醇引起的神经元AA释放。谷氨酸能够协同乙醇引起的AA释放,NMDA受体拮抗剂MK-801能够抑制乙醇引起的AA释放,并且低于基础释放水平。结论乙醇可能通过与谷氨酸有关的氧化机制影响神经细胞AA的释放,原花青素参与调节乙醇引起的AA释放作用。
2008年S1期 v.25 134页 [查看摘要][在线阅读][下载 5K] [下载次数：114 ] |[网刊下载次数：0 ] |[引用频次：0 ] |[阅读次数：152 ] 下载本期数据