卡维地洛对梗死心脏心肌连接蛋白43的影响

Influence of carvedilol on gap junctional connexin 43 in infarcted myocardium

目的探讨卡维地洛对梗死心脏心肌组织连接蛋白43的影响。方法结扎大鼠左冠状动脉建立心肌梗死模型。随机将大鼠分为假手术组、手术组和手术加卡维地洛组。术前7d分别用安慰剂、卡维地洛(日剂量2mg/kg,分2次给药)。术后1,3,7d检测左心室游离壁、室间隔、右心室壁连接蛋白43表达,术后7d测心肌梗死病灶大小、室间隔厚度、左心室大小。结果连接蛋白43表达于心肌梗死1～7d呈逐渐增加趋势;左心室游离壁连接蛋白43表达于心肌梗死1～7d时均处于低水平,与对照组差异有统计学意义(P<0.05);右心室壁连接蛋白43表达于心肌梗死1～7d与对照组差异无统计学意义(P>0.05)。卡维地洛能明显地抑制缺血肥厚心肌组织连接蛋白43的上调,抑制左心室扩张和缩小心肌梗死病灶。结论心肌梗死肥厚组织中连接蛋白43上调,卡维地洛能减轻心肌重构与选择性的抑制肥厚心肌组织中的连接蛋白43上调有关。

Objectives To investigate the influence of earvedilol on gap junctional eonnexin 43 （Cx43） in infarcted rat myoeardium. Methods Rat myocardial infarction model was established by permanent ligation of the left coronary artery, infarcted rats were orally treated with placebo, or earvedilol （2 mg·kg^-1·d^-1） at beginning 7 days before induction of myocardial infarction. Cx43 was measured at 1^st, 3^rd and 7^th days post coronary occlusion in both noninfareted and infarcted myoeardium. Infarcted size and left ventrieular dilation were determined in pierosirius red stained hearts. Results Myocardial infarction induced an up regulation of Cx43 protein in the hypertrophied interventrieular septal （IS）（maximum at day 7 post infarction） , whereas Cx43 protein expression of Cx43 was decreased greatly in the infarcted myoeardium of left ventrieular free wall （LVFW） at 1^st, 3^rd and 7^th day post infarction, there were significant differences compared with control （P〈 0.01）. Carvedilol inhibited protein up-regulation of Cx43 and thickness of interventrieular septal, decreased left ventrieular dilation and reduced infarct size more obviously. Conclusions Infarction-induced eardiae hypertrophy was accompanied by an up-regulation of Cx43 in IS, whereas Cx43 was down-regulated in LVFW in the processing of cardiac infarcted pathogenesis. Carvedilol differentially reduced post infarction remodeling associated with selective inhibition of eardiae Cx43 in hypertrophied myoeardium.