Ghrelin对慢性充血性心力衰竭兔三层心肌间Cx43表达的影响Effect of Ghrelin on the expression of Cx43 in three layers in rabbit with chronic congestive heart failure
李思瑶;陆士娟;吴美霞;吴淼;马添翼;李强;张伟;黄康;钟江华;
摘要(Abstract):
目的观察生长激素释放肽(ghrelin)对慢性充血性心力衰竭(chronic congestive heart failure,CHF)兔左心室三层心肌间跨室壁缝隙连接蛋白43(connexin43,Cx43)表达的影响,为CHF恶性室性心律失常(malignant ventricular arrhythmia,MVA)的防治寻找新的靶点。方法将40只新西兰大白兔随机分成假手术组(Sham组,n=20)和CHF组(n=20)。CHF组通过缩窄腹主动脉构建CHF模型,sham组开腹未结扎。术后同等条件喂养8周,在体检查超声心动图比较两组兔左心室舒张末期内径(left ventricular end-diastolic diameter,LVEDD)、左室后壁厚度(left ventricular posterior wall thickness,LVPW)和左室射血分数(left ventricular ejection fraction,LVEF);在体血流动力学检查比较两组心率(heart rate,HR)、外周动脉收缩压(peripheral arterial systolic pressure,SBP)、舒张压(diastolic blood pressure,DBP)、平均动脉压(mean arterial pressure,MAP)、左心室最大上升速度和最大下降速度(±dp/dt_(max))等参数。饲养8周后将Sham组分成Sham台式液灌流亚组、Sham Ghrelin灌流亚组,CHF组分成CHF台式液灌流亚组、CHF ghrelin灌流亚组,处死兔制作左心室心肌Masson染色图片,分别给予正常台式液及ghrelin对CHF组及Sham组的心脏灌流,分别切取左心室心内膜下心肌(endometrium,endo)、中层心肌(middle,mid)、心外膜下心肌(epicordium,Epi),采用RT-PCR、Western blot检测各组左心室三层心肌间Cx43mRNA(Cx43-Cq)、Cx43蛋白(Cx43-pro)的表达,并计算三层心肌间最大Cx43-pro与最小Cx43-pro之差(ΔCx43-pro)以及最大Cx43-Cq与最小Cx43-Cq之差(ΔCx43-Cq)。结果与Sham组相比,CHF组P、SBP、DBP、MAP明显升高,LVEF明显下降(P<0.05)。与Sham台式液灌流亚组相比,CHF台式液灌流亚组三层心肌的Cx43蛋白及mRNA的表达明显降低(P<0.05)。CHF组内相比,CHF Ghrelin灌流亚组的Cx43蛋白及mRNA的表达明显高于CHF台式液灌流亚组,而△Cx43-pro及△Cx43-Cq显著低于CHF台式液灌流亚组(P<0.05)。结论 CHF兔左心室三层心肌间的Cx43蛋白发生重构,含量明显减少,而ghrelin离体心脏灌流能改善慢性充血性心力衰竭兔Cx43蛋白的重构。
关键词(KeyWords): 慢性充血性心力衰竭;中层心肌细胞;连接蛋白43;生长激素释放肽;恶性室性心律失常
基金项目(Foundation): 国家自然科学基金资助项目(81660057)
作者(Author): 李思瑶;陆士娟;吴美霞;吴淼;马添翼;李强;张伟;黄康;钟江华;
Email:
DOI: 10.14066/j.cnki.cn21-1349/r.2019.1232
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