Effect of Total Flavones in Clematis Filamentosa Dunn against Myocardial Ischemia Reperfusion Injury by Adjusting Autophagy in Rats

Abstract

AIM To study the effect of total flavones of Clematis Filamentosa Dunn(TFCD) on adjusting autophagy against myocardial ischemia-reperfusion injury (MIRI). METHODS Forty male SD rats were divided randomly into five groups(n=8): sham group, model group(I/R), TFCD treatment group(TFCD), autophagy activator rapamycin treatment group(Rap) and TFCD+ rapamycin treatment group(TFCD+Rap). While Myocardial ischemia-reperfusion injury model was established by ligation of left anterior descending coronary artery (LAD) in rats. Hemodynamic indexes of heart were recorded, myocardial infarction area was observed, and serum lactate dehydrogenase (LDH), creatine kinase isoenzyme (CK-MB), total antioxidant capacity (T-AOC), nitric oxide (NO), inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) were measured. The content of Caspase-3 and the activity of Caspase-3 were measured. The protein expression of autophagy associated genes LC3-II and Beclin1 in myocardium was detected by using RT-PCR and Western blot. RESULTS TFCD treatment remarkably improved hemodynamics function, reduced myocardial infarct size, enhanced the contents of T-AOC, NO and eNOS, decreased the contents of LDH, CK-MB, iNOS and the activity level of caspase-3(P<0.05 or P<0.01). In addition, TFCD treatment significantly inhibited the expression of autophagy-related proteins LC3-II and Beclin-1. Autophagy activator inhibited the effect of TFCD. CONCLUSION The cardioprotection of TFCD against myocardial ischemia reperfusion injury may be mediated through improving antioxidant, regulating NO, reducing apoptosis and inhibiting autophagy.