辛伐他汀对大鼠心肌缺血再灌注后细胞凋亡及线粒体融合素2表达的影响

The effect of Simvastatin on cardiomyocyte apoptosis and Mitofusin 2 expression after myocardial ischemia/reperfusion injury in rats

目的:探讨辛伐他汀对大鼠心肌缺血再灌注后细胞凋亡及线粒体融合素2(Mitofusin 2,Mfn2)表达的影响。方法:选取32只Sprague-Dawley(SD)大鼠,随机分为假手术组、缺血再灌注模型组(模型组)、5 mg辛伐他汀组、10 mg辛伐他汀组,每组8只。5 mg辛伐他汀组、10 mg辛伐他汀组分别于术前7 d开始给予5 mg/(kg·d)、10 mg/(kg·d)的辛伐他汀灌胃,假手术组、模型组均给予等量蒸馏水灌胃。采用结扎左前降支法建立大鼠心肌缺血再灌注损伤模型。各组于造模后3 h剪取心脏组织,采用TUNEL法检测心肌细胞凋亡,Western Blot法检测p-Akt的表达,免疫组织化学法检测Mfn2的表达。结果 :与假手术组相比较,模型组心肌细胞凋亡指数、Mfn2的表达明显升高,p-Akt的表达显著降低(均P<0.05);与模型组比较,5 mg辛伐他汀组、10 mg辛伐他汀组心肌细胞凋亡指数、Mfn2的表达显著降低,p-Akt的表达显著升高(均P<0.05),并显示出明显剂量依赖性(P<0.05)。结论:辛伐他汀可有效抑制心肌缺血再灌注损伤后的心肌细胞凋亡,抑制Mfn2表达是其可能作用机制。

Objective： To evaluate the effect of Simvastatin on cardiomyocyte apoptosis and Mitofusin 2（Mfn2） expression after myocardial ischemia-reperfusion injury in rats. Methods： 32 Sprague-Dawley（SD） rats were randomly divided into shamoperation group, ischemia-reperfusion model group（model group） 5 mg Simvastatin group and 10 mg Simvastatin group, 8 rats in each group. The 5 mg Simvastatin group and 10 mg Simvastatin group respectively were given 5 mg/（kg·d） or 10 mg/（kg·d）Simvastatin gavage before preoperative 7 d. The sham-operation group and model group were given to equivalent normal saline gavage. The myocardial ischemia-reperfusion injury model were induced by ligation of left anterior descending artery.3 h after reperfusion, the hearts of each group rats were harvested. The cardiomyocyte apoptosis was detected by TUNEL method, the p- Akt expression was detected by Western Blot, and the Mitofusin2（ Mfn2） expression was detected by immunohistochemistry method. Results： Compared with sham-operation group, the cardiomyocyte apoptosis index and Mfn2 expression of model group were significantly increased, and the p-Akt expression significantly decreased（P〈0.05）. Compared with model group, the cardiomyocyte apoptosis index and Mfn2 expression of 5 mg Simvastatin group and 10 mg Simvastatin group significantly decreased, and the p- Akt expression significantly increased（ P〈0. 05）, and showed significantly dose-dependent manner（ P〈0. 05）. Conclusion ： Simvastatin can inhibit the cardiomyocyte apoptosis after myocardial ischemia-reperfusion injury, and down-regulated expression of Mfn2 may be its mechanism.