吴岚,李鹏飞,林继红,包凯,张为革
WU Lan1,LI Peng-fei1,LIN Ji-hong1,BAO Kai2,ZHANG Wei-ge2 (1.Department of Geriatrics

• 1:中国医科大学附属第一医院
• 2:中国医科大学附属第一医院
• 3:中国医科大学附属第一医院
• 4:沈阳药科大学制药工程学院

摘要(Abstract)：

目的通过观察红霉素衍生物LY267108对单核细胞增殖和核因子-κB(NF-κB)表达的影响,探讨红霉素衍生物抗炎作用的机制。方法以红霉素为对照,用四氮唑盐(MTT)还原法观察LY267108对单核细胞增殖的影响;用反转录-聚合酶链式反应(RT-PCR)和Western Blot方法观察LY267108对单核细胞NF-κB表达的影响。结果LY267108和红霉素均可抑制单核细胞的增殖,其IC50值分别为154.9、493.4μmol.L-1;RT-PCR和Western Blot测定结果显示LY267108可抑制单核细胞NF-κB mRNA和蛋白的表达,并与剂量之间呈现负相关。结论红霉素衍生物LY267108的抗炎活性可能与其抑制炎症细胞增殖和影响NF-κB活化有关。
Objective To observe the effects of erythromycin derivative LY267108 on the proliferation and the expression of nuclear factor-kappa B(NF-κB)of monocyte and study the anti-inflammatory mechanism of erythromycin derivatives.Methods The effects of LY267108 on the proliferation were evaluated by monotetrazolium test assay(MTT assay);monocytes were exposed to 100 pmol·L-1 TNF-α with or without pretreatment with 3,10,30 or 100 mg·L-1 of LY267108 1 h at 37 ℃.The expression of NF-κB was observed by reverse transcription-polymerase chain reaction(RT-PCR) and by Western Blot.Results The proliferation of monocyte was inhibited by LY267108 and erythromycin with IC50 of 154.9 μmol·L-1 and 493.4 μmol·L-1,respectively;LY267108 decreased the expressions of NF-κB mRNA and protein in a dose-related fashion.Conclusions The anti-inflammatory activity of erythromycin derivatives maybe due partly to the interaction with the proliferation and NF-κB signaling pathway in inflammatory cells.

关键词(KeyWords)： 红霉素衍生物;抗炎活性;单核细胞;增殖;核因子-κB
erythromycin derivative;anti-inflammatory activity;monocyte;proliferation;nuclear factor-kappa B

Abstract:

Keywords:

基金项目(Foundation): 沈阳市科技计划技术创新开发基金资助项目(1053125-1-49)

作者(Author): 吴岚,李鹏飞,林继红,包凯,张为革
WU Lan1,LI Peng-fei1,LIN Ji-hong1,BAO Kai2,ZHANG Wei-ge2 (1.Department of Geriatrics

参考文献(References)：

• [1]DAVIDSON R,PELOQUIN L.Anti-inflammatory ef-fects of the macrolides[J].J Otolaryngol,2002,31(sup-pl 1):S38-40.
• [2]KEICHO N,KUDOH S.Disffuse panbronchiolitis:Roleof macrolides in therapy[J].Am J Respir Med,2002,1(2):119-131.
• [3]KIBWAGE I O,JANSSEN G,BUSSON R,et al.Translactonization in erythromycins[J].J Org Chem,1987,52(19):990-996.
• [4]JOHNSTON S L.Macrolide antibiotics and asthmatreatment[J].J Allergy Clin Immunol,2006,117(6):1233-1236.
• [5]CAZZOLA M,SALZILLO A,DIAMARE F.Potentialrole of macrolides in the treatment of asthma[J].Monaldi Arch Chest Dis,2000,55(3):231-236.
• [6]SAKITO O,KADOTA J,KOHNO F,et al.Interleukin1 beta,tumor necrosis factor alpha,and interleukin 8 inbronchoalveolar lavage fluid of patients with diffuse pan-bronchiolitis:A potential mechanism of macrolide thera-py[J].Respiration,1996,63(1):42-48.
• [7]SCHULTZ M,SPEELMAN P,ZAAT S,et al.Ery-thromycin inhibits tumour necrosis factor alpha killedand interleukin 6 production induced by heat-killedStreptococcus pneumoniaein whole blood[J].Antimi-crob Agents Chemother,1998,42(7):1605-1609.