葛根素预处理保护心肌缺血再灌注损伤的机制

The Mechanism of Protective Effect of Puerarin on Myocardial Ischemic Reperfusion Injury in Rats

目的:探讨线粒体ATP敏感性钾通道(mitoKATP)是否参与葛根素(puerarin,PUE)预处理保护心肌缺血再灌注损伤的机制。方法:开胸结扎左冠状动脉前降支(LAD),复制大鼠心肌缺血再灌注损伤模型,设立假手术(sham)组、缺血再灌注(I/R)组、PUE预处理组,PUE预处理加mitoKATP特异性阻断剂5-hydroxydecanoate(5-HD)组和5-HD组,采用TTC法测定心肌梗塞面积,TUNEL法检测心肌细胞凋亡情况,并测定血清肌酸激酶(CK)活力。结果:I/R组较sham组心肌梗塞面积、血清CK活力以及心肌细胞凋亡指数显著增高;与I/R组比较,PUE预处理组心肌梗塞面积明显缩小,血清CK活力和心肌细胞凋亡指数显著降低;PUE加5-HD组与PUE预处理组相比心肌梗塞面积增大,心肌细胞凋亡增加,血清CK活力增高;5-HD组与I/R组相比以上指标差异均无显著意义。结论:葛根素预处理明显减轻了大鼠心肌I/R损伤,其心肌保护效应可能部分通过开放mitoKATP通道的途径产生。

Objective： To investigate the role of mitoehondrial KATP channel （mitoKATP） in the protective effect of puerarin （PUE） on myocardial ischemia-reperfusion injury in rats. Methods： Rat heart ischemia-reperfusion injury （I/R） models were induced by occluding the left anterior descending coronary artery for 45 min and reperfusion for 120 min. Fifty-five rats were randomly divided into five groups （ 11 in each）： （1） Group sham （did not receive operation）; （2） group I/R; （3） group PUE （received PUE at a dose of 100 mg/kg intravenously 5 min before ischemia） ;（4） group P5D （received 5-hydroxydecanoate, a mitoKATP specific inhibitor, at a dose of 5 mg/kg intravenously 15 min before ischemia and PUE treatment at 5 min before ischemia） ; and （5） group 5-HD （received 5-hydroxydecanoate alone 15 minutes before ischemia）. TTC dyeing was used to determine the myocardial infarction size. Cardiac myocytes apoptosis was detected by using TUNEL. Creatine kinase activity （CK） in serum was measured simultaneously. Results： Infarct size, cardiomyocytes apoptosis and CK activity in serum of group I/R were obviously higher than those in group sham （P 〈0. 05 or P 〈0. 01）. Compared with group I/R, all these parameters in PUE groups were significantly lower （P 〈0. 05 or P 〈0. 01 ）. While, in group PSD, all these parameters were significantly higher than those in group PUE. There was no significant difference found among the parameters of groups PSD, I/R and 5-HD. Conclusions： Preconditioning with puerarin can significantly reduce myocardial ischemia-reperfusion injury in rats. The protective effect of puerarin to myocardium is partly via opening the mitoKATP channel.