尼可地尔后处理对急性缺血诱导的大鼠心肌细胞凋亡的影响

The Effects of Nicorandil Postconditioning on Ischemia-Induced Cardiomyocyte Apotosis in Acute Myocardial Ischemia Rats

目的探讨尼可地尔后处理对大鼠心肌缺血再灌注损伤的保护作用及机制。方法SD大鼠随机分为6组:假手术组、缺血再灌注组、缺血后处理组、尼可地尔后处理2、5和10 mg/kg剂量组。采用左冠状动脉前降支结扎30 min、再灌注120 min建立大鼠心肌缺血再灌注模型。缺血后处理组在缺血后再灌注前实施5次10 s再灌注—10 s再阻断循环。尼可地尔后处理组在缺血后再灌注前分别给予三个剂量10 min。检测血清肌酸激酶和丙二醛含量,及超氧化物歧化酶活性;检测心肌细胞的凋亡率和Caspase-3蛋白的表达。结果尼可地尔后处理能使肌酸激酶、丙二醛含量降低,超氧化物歧化酶活性增高,心肌细胞凋亡率降低,Caspase-3蛋白表达减少。结论尼可地尔后处理对缺血再灌注损伤的心肌具有保护作用,其机制可能与提高超氧化物歧化酶活性,增强心肌抗氧化能力,减轻氧自由基损伤,稳定细胞膜,抑制细胞凋亡有关。

Aim To study the effect and possible mechanism of nicorandil postconditioning on myocardial ischemia reperfusion（MIR） injury in rats. Methods The SD rats were randomly divided into six groups： control group,ischemia reperfusion group,postconditioning group,nicorandil postconditioning groups of 2 mg/kg,5 mg/kg,and 10 mg/kg.Ischemia reperfusion group was obtained by ligated left anterior descending coronary artery 30 minutes and followed by 120 minutes reperfusion.Postconditioning group was obtained by 5 cycles of brief 10 seconds intermittent reperfusion/reocclusion.After 30 minutes ischemia,hearts were exposed to nicorandil for 10 minutes immediately at the onset of reperfusion.Contents of creatine kinase（CK） and malondialdehyde（MDA）,activity of superoxide dismutase（SOD） were detected respectively.Apoptosis rates and the expression of caspase-3 were investigated. Results In the nicorandil postconditioning groups,contents of CK and MDA were lower,activities of SOD were higher,apotosis rates were decreased,and caspase-3 was lower. Conclusions Nicorandil postconditioning could protect MIR.The myocardial protective mechanism maybe realized by enhancing the activity of SOD,enhancing myocardial antioxygen capability,reducing the oxygen free radical injury,stabilizing myocardial cellular membrance and inhibition of apoptosis.