阿托伐他汀干预减轻缺血复合冷应激诱导的大鼠心肌损伤

 摘要：目的 分析缺血复合冷应激对大鼠心肌的影响，探讨阿托伐他汀干预对这种复合应激下心肌的作用及可能机制。方法 以永久性左冠状动脉前降支结扎术+4℃冷刺激（8小时/天，4天）建立心肌缺血复合冷应激大鼠模型，复合应激前3天及后4天给以阿托伐他汀灌胃（20mg.kg-1.d-1）。超声心动图评价心功能，TTC染色法测定心肌梗死面积，western blotting法检测心肌p-PI3K、p-GSK3β、Bim、Caspase3蛋白表达。结果 心肌缺血复合冷应激使心功能恶化、梗死面积增大(P<0.01)；阿托伐他汀干预后心功能改善、梗死面积缩小(P<0.01), p-PI3K、p-GSK3β表达上调(P<0.01)，Bim、Caspase3表达下降(P<0.01)。结论 心肌缺血复合冷应激加重心肌损伤，阿托伐他汀干预能部分减弱此作用，其机制可能与激活PI3K/Akt/GSK3β通路及下调Bim表达有关。

Effect of atorvastatin on myocardial injury in rats following co-stress of myocardial ischemia and cold

Abstract: Objective To analyze the effect of co-stress of myocardial ischemia(MI) and cold on myocardium in rats,and investigate the role and relative mechanism of atorvastatin intervention in such co-stress.Methods Co-stress model was induced by ligation of left coronary artery combined with cold stress of 4℃,8h/d for 4 consecutive days.Rats were gavaged with atorvastatin 20mg.kg-1.d-1 for 3 days before MI was induced and thereafter for 4 days.Cardiac function was assessed by echocardiography;myocardial infarct size was determined by TTC staining;p- PI3K,p-GSK3β,Bim and Caspase-3 expression in myocardium was determined by western blotting.Results It was demonstrated that co-exposure of myocardial ischemia and cold stress could significantly deteriorate the cardiac function and increase the infarct size (P<0.01),and this was attenuated by atorvastatin use with increased expression of p-PI3K,p-GSK3β and Bim, Caspase3 downregulating(P<0.01).Conclusion Co-exposure to myocardial ischemia and cold stress aggravate the cardiac injury, this influence can partially attenuated by atrovastatin use and the mechanism may be attributed to activation of PI3K/Akt/GSK3β and decreasing expression of Bim.