缺血性心肌病大鼠心肌细胞自噬在心肌重塑中的作用

The relationship between myocardial remodeling and endoplasmic reticulum stress and autophagy in rats with ischemic cardiomyopathy

目的:研究缺血性心肌病大鼠心肌细胞自噬在心肌重塑中的作用。方法:36只雄性SD大鼠分为正常对照组、假手术组、缺血性心肌病组(n=12),3组大鼠术前行心脏彩超检查,正常对照组大鼠不进行处理;假手术组大鼠开胸后不结扎冠状动脉,关闭胸腔;缺血性心肌病组大鼠开胸结扎冠状动脉20 min后,解开结扎线行再灌注后关闭胸腔,3组大鼠术后4周行心脏彩超检查后处死大鼠取心脏行HE染色、masson染色,观察心肌病理改变,用Western blot技术检测各组大鼠心肌细胞GRP78、LC3-Ⅰ、LC3-Ⅱ、Beclin-Ⅰ表达及LC3-Ⅱ/LC3-Ⅰ比值的变化。结果:与正常组及假手术组比较,缺血性心肌病大鼠心室扩大,EF值降低;心肌排列紊乱,心肌纤维化增加;线粒体空泡化严重;内质网应激关键蛋白GRP78上调;自噬相关蛋白LC3-Ⅰ、LC3-Ⅱ、Beclin-Ⅰ及LC3-Ⅱ/LC3-Ⅰ比值增加。结论:缺血性心肌病大鼠心肌细胞中内质网应激和自噬可能在心肌重塑中具有重要作用。

Objective: To study the relationship between myocardial remodeling and endoplasmic reticulum stress and autophagy in rats with ischemic cardiomyopathy. Methods: Thirty-six male SD rats were divided into normal control group,sham-operated group and ischemic cardiomyopathy group(n = 12). Echocardiography was performed before operation in three groups. Rats in sham-operated group closed their thoracic cavity without ligation of coronary artery after thoracotomy. The rats in ischemic cardiomyopathy group were closed their thoracic cavity after ligating of coronary artery for 20 minutes and recovered reperfusion. After operation for 4 weeks,rats in three groups were killed after taking echocardiography. The myocardial tissues were taken for HE staining and Masson staining to observe the pathological changes of myocardium and the expressions of glucose-regulated protein 78(GRP78),microtubule-associated protein 1 light chain 3-Ⅰ(LC3-Ⅰ),microtubule-associated protein 1 light chain 3-Ⅱ(LC3-Ⅱ),Bcl-2 interacting protein(Beclin-Ⅰ)and the ratio of LC3-Ⅱ/LC3-Ⅰ were detected by Western blot. Results: Compared with normal group and sham-operated group,ischemic cardiomyopathy rats had significant differences in echocardiography and myocardial pathology;the myocardial array was disordered,myocardial fibrosis was increased,mitochondrial vacuolation was serious. Mean while,the expressions of GRP78,LC3-Ⅰ,LC3-Ⅱ,Beclin-Ⅰ and LC3-Ⅱ/LC3-Ⅰ ratio had significant changes. Conclusion: Autophagy and endoplasmic reticulum stress may play important roles in myocardial remodeling in rats with ischemic cardiomyopathy.