Study on the Effect of Zhenwu Tang on PINK1/Parkin Mediated Mitochondrial Autophagy in Rats with Chronic Heart Failure

LIAO Jinhua; WANG Xing; WANG Xiaoling; CHEN Zhiyong; CHE Chi; SHAN Haohong; LI Lin

Abstract：Objective To explore the effects and mechanisms of Zhenwu Tang in treating chronic heart failure (CHF) rats from mitochondrial autophagy.Methods 60 SD male rats were randomly divided into 6 groups:sham-operated group,model group,Losartan group,Zhenwu Tang 6 g/kg group,Zhenwu Tang 12 g/kg group,Zhenwu Tang 18 g/kg group;and the rat model of CHF was established by using the ligation method of the anterior descending branch of the left coronary artery (left Anterior descending artery,LAD).After 56 days of model induction and 28 days of gavage,various tests were conducted to evaluate different aspects of cardiac function.M-mode echocardiography (ME) was used to assess cardiac function,ELISA was performed to measure serum B-type natriuretic peptide (BNP) levels,HE staining and transmission electron microscopy were employed to observe myocardial structure and mitochondrial ultrastructural changes.Additionally,Western blot analysis was conducted to detect the expression levels of PTEN-induced putative kinase 1 (PINK1),E3 ubiquitin protein ligase ( parkin),phosphorylated PINK1 ( p-PINK1),phosphorylated parkin ( p-parkin),microtubule-associated protein 1 light chain (LC3),SQSTM1 protein (p62),and Beclin1 protein.Results Compared with the sham-operated group,the systolic and diastolic functions of the rat hearts in the model group were significantly attenuated (P<0.05).The expressions of p-PINK1,p-parkin and Beclin1 and LC3 Ⅱ/Ⅰ were significantly decreased (P<0.05).While the expression of p62 was significantly increased (P<0.05),and the myocardium showed small-patch fibrosis,disorganised arrangement of myocardial contractile bands,and shallower and fewer mitochondrial matrix,Compared with the model group,BNP level and p62 expression were significantly decreased in Zhenwu Tang 6 g/kg group,Zhenwu Tang 12 g/kg group and Zhenwu Tang 18 g/kg group (P<0.05) The expression of p-parkin,p-PINK1 and Beclin1 as well as LC3 Ⅱ/Ⅰ increased significantly (P<0.05),and the systolic and diastolic functions of the heart improved significantly (P<0.05).The systolic and diastolic functions of the heart were significantly improved (P<0.05),the degree of myocardial fibrosis decreased,myocardial arrangement was more regular,mitochondrial matrix was full and mitochondrial cristae were intact.Conclusion Zhenwu Tang can activate PINK1/parkin-mediated mitochondrial autophagy,enhance the utilization of substances in damaged mitochondria,improve the energy supply to the myocardium,ameliorate the cardiac function and myocardial structure of CHF rats,and inhibit the process of CHF.