美托洛尔对大鼠心肌梗死周边区缝隙连接蛋白43的影响

目的:探讨美托洛尔对大鼠心肌梗死(心梗)后梗死周边区缝隙连接蛋白43(Cx43)的影响。方法:80只大鼠随机分为假手术组(20只)、心梗组(30只)和美托洛尔组(30只),用结扎冠状动脉左前降支的方法制备心梗模型,美托洛尔组给予美托洛尔5mg/(kg.d)灌胃,心梗组给予安慰剂。手术8周后,测量梗死周边区心室颤动阈值(室颤阈值)。用蛋白印记分析和RT-PCR分别观察心梗后梗死周边区缝隙连接蛋白43(Cx43)磷酸化的蛋白质及总量表达和mRNA表达的变化;免疫荧光法观察梗死周边区Cx43的分布。结果:8周后,美托洛尔组室颤阈值高于心梗组[(11.0±2.65)V比(7.1±4.1)V,P<0.05],美托洛尔组Cx43磷酸化的蛋白质及总量均显著高于心梗组,Cx43mRNA的表达也明显高于心梗组。Cx43的密度和分布均显著高于心梗组。结论:美托洛尔能显著改善梗死周边区缝隙连接重构,这可能是美托洛尔能够抑制心梗后室性心律失常的一个机制。

Effect of Metoprolol on Connexin43 Expression in Infarcted Border Zone of Rat Myocardium

Objective:To investigate the effect of metoprolol on the expression of connexin43 (Cx43) infarcted border zone of myocardium after myocardial infarction (MI) in rats. Methods: Eighty rats were randomly assigned into three groups: MI group (n=30, the left anterior descending coronary artery was ligated), metoprolol group (n=30, rats with MI were treated with metoprolol), and sham-operation group (n=20). Eight weeks after surgery, ventricular fibrillation threshold (VFT) was measured in infarcted border zone. Western blot and RT-PCR were adopted respectively to determine the expression of Cx43 protein and mRNA in infarcted border zone, respectively. Immunofluorescence analysis for observing changes of Cx43 protein distribution in infarcted border zone. Results: Eight weeks after ligation, VFT was higher in metoprolol group than in MI group significantly ([11.0±2.65] V vs [7.1±4.1]V, P<0.05). Compared with the MI group, both the percentage of phosphorylated Cx43 and the total content of Cx43 of the metoprolol group were markedly increased. The level of Cx43 mRNA in the metoprolol group also increased notablely. Immunofluorescence showed that ischemia can induce the redistribution of Cx43 and metoprolol ameliorated Cx43 redistribution after MI. Conclusion: Metoprolol can effectively ameliorate the expression and distribution of Cx43 in infarcted border zone of rat myocardium after MI.