曲美他嗪对心肌梗死后心力衰竭大鼠心肌自噬水平的影响

摘要

目的 观察心肌梗死(MI)后心力衰竭(心衰)大鼠应用曲美他嗪后左心功能及心肌自噬水平的变化.方法 健康雄性Wistar大鼠20只结扎左冠状动脉前降支近段,4周后随机分为模型组(M组)、曲美他嗪组(Q组),每组10只,另设假手术组(S组)10只,Q组给予曲美他嗪15 mg·kg-1·d-1,用药4周后,使用小动物超声仪检测左室心功能水平,PV-Loop压力-容积系统测量大鼠血流动力学水平,酶联免疫吸附试验测定(ELISA)法检测大鼠血清N-末端脑钠肽前体(NT-proBNP)和超敏肌钙蛋白T(hs-TnT)水平,HE和Masson染色观察心肌病理学改变和纤维化情况,TUNEL荧光染色检测心肌细胞凋亡情况,Western blot法和RT-PCR检测心肌组织自噬相关蛋白和基因的表达水平.结果(1)曲美他嗪显著改善了大鼠MI后心衰引起的左室扩张和功能障碍.(2)曲美他嗪显著改善了心衰引起的压力负荷加重、左室顺应性降低.(3)曲美他嗪减轻了心衰大鼠心肌细胞水肿、坏死以及心肌纤维化.(4)ELISA结果显示,曲美他嗪显著改善了大鼠心衰引起的血清NT-proBNP和hs-TnT水平升高.(5)曲美他嗪降低了心衰引起的心肌细胞凋亡.(6)Western blot和RT-PCR结果显示,曲美他嗪可上调心衰大鼠心肌自噬水平,并且增加心肌自噬流的活化.结论 自噬对心肌细胞有保护作用,曲美他嗪可通过上调MI后心衰大鼠心肌细胞自噬水平,改善心功能.%Objective To observe changes of left ventricular function and the level of autophagy after treatment with trimetazine in rats with heart failure after myocardial infarction(MI). Methods Twenty healthy male Wistar rats with the ligation of the proximal part of the left descending branch were randomly and equally allocated into two groups,model group (M group) and trimetazine group (Q group). A sham group (S group) was made up by 10 sham-operated rats. Rats of trimetazine group were given trimetazine(15 mg/kg)once a day for 4 weeks.Then left ventricular function was measured by echocardiography,and hemodynamics was evaluated by Millar pressure-volume system.Serum levels of NT-proBNP and hs-TnT were tested by ELISA.Pathological changes and fibrosis of myocardium were observed by HE and Masson staining.The myocardial apoptosis level was observed by TUNEL, and expressions of autophagy related protein and gene in myocardial tissue were detected by Western blot assay and RT-PCR. Results Trimetazine treatment significantly improved left ventricular dilatation and dysfunction in rats with myocardial failure. Trimetazine treatment also significantly improved pressure overload and the compliance decrease of left ventricular in rats with heart failure after myocardial infarction. Trimetazidine reduced the edema,necrosis and myocardial fibrosis of cardiac myocytes in rats with heart failure.The results from ELISA showed that serum levels of NT-proBNP and hs-TnT were significantly lower in the trimetazine group than those of model group.Compared with model group,the cardiomyocyte apoptosis decreased significantly in the trimetazine group.The results from Western blot assay and RT-PCR showed that autophagic flow of myocardium was increased remarkably in the trimetazine group than that of model group. Conclusion Autophagy has a protective effect on myocardial cells. Trimetazine can improve cardiac function through up-regulation of autophagy in cardiomyocytes in MI rats with heart failure.