Effects of trimetazidine on myocardial autophagy in rats with heart failure after myocardial infarction / 天津医药

ABSTRACT

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.