Protective Effect of Trimetazidine against Autophagy-induced Myocardial Ischemia-reperfusion Injury in Rats / 中国医科大学学报

ABSTRACT

Objective To observe the protective effects of trimetazidine against myocardial ischemia-reperfusion (I/R) injury in rats and relationship with the autophagy-related protein,microtubule-associated protein light chain 3 protein-Ⅱ (LC3-Ⅱ) and another autoclaved marker sequestosome 1 (p62) as well as to investigate the mechanism of action.Methods Fifty-four male SD rats were randomly divided into three groups with 18 rats in each groupsham group,myocardial I/R group,and TMZ plus myocardial I/R group.The rats in each group were sacrificed at model completion,and 4 and 8 weeks later.RT-PCR and Western blotting were performed to determine the levels of LC3-Ⅱ and p62.The morphological changes in the myocardium were observed by HE staining.Results Compared with the sham group,the I/R group demonstrated increased expression of LC3-Ⅱ and p62 (P ＜ 0.05).Compared with that in the I/R group,the expression of LC3-Ⅱ and p62 in the I/R + TMZ group decreased (P ＜ 0.05).The expression of LC3-Ⅱ and p62 increased at week 4 (P ＜ 0.05).At week 8,the expression levels of LC3-Ⅱ and p62 decreased in cardiomyocytes (P ＜ 0.05).Conclusion Intervention with trimetazidine may protect the myocardium of rats against ischemia-reperfusion injury by regulating autophagy and the effect is maintained for a certain period.