新加温胆汤调控AMPK/SIRT1/PGC-1α通路干预高脂血症伴心肌缺血OA

Objective To investigate the mechanism of Modified Wendan Decoction in intervening hyperlipidemia complicated with myocardial ischemia by modulating energy metabolism through the AMP-activated protein kinase(AMPK)/sirtuin 1(SIRT1)/peroxisome proliferatoractivated receptor gamma coactivator 1-alpha(PGC-1α)signaling pathway.Methods Thirty SPF SD rats were randomly divided into the blank group,the model group,the Wendan Decoction group,the Modified Wendan Decoction group,and the trimetazidine group,6 in each group.Except for the blank group,the other groups received a high-lipid diet for 6 weeks to establish the hyperlipidemia model of rats,and then the corresponding drugs were administered for 14 days.One hour after the final administration,the myocardial ischemia model was induced via intraperitoneal injection of pituitrin,except the blank group.Electrocardiogram was used to detect changes in cardiac electrical activity;HE staining was utilized to assess pathological modifications in rat myocardium;ELISA was conducted to evaluate changes in serum levels of myocardial injury markers creatine kinase-myocardial band(CK-MB),cardiac troponin I(cTnI),and myoglobin(MYO);the levels of total cholesterol(TC),triglycerides(TG),superoxide dismutase(SOD),and malondialdehyde(MDA)in serum,as well as adenosine triphosphate(ATP),Na+K+-ATP,and Ca2+-ATP in myocardial tissue were measured using colorimetry.The mRNA expressions of AMPK,SIRT1,and PGC-1α in myocardial tissue were quantified through Real-time PCR.The AMPK,p-AMPK,SIRT1,and PGC-1α protein expressions in myocardial tissue were analyzed via Western Blot.Results The model group rats showed significant J-point deviation,T-wave elevation,increased heart rate,disrupted myocardial fibers,and disordered cell arrangement;these pathological manifestations were ameliorated to varying degrees in all intervention groups.Compared to the blank group,the model group showed increased J-point deviation and elevated serum levels of CK-MB,cTnI,MYO,TC,TG,and MDA,while serum SOD levels,myocardial ATP content,Na+K+-ATPase and Ca2+-ATPase activities,and AMPK,SIRT1,and PGC-1α mRNA and protein expression were decreased(P＜0.05,P＜0.01).Compared with the model group,the intervention groups showed decreased J-point deviation and lower serum CK-MB,cTnI,and MYO levels,while serum SOD levels,myocardial ATP content,Na+K+-ATPase and Ca2+-ATPase activities,myocardial SIRT1 mRNA expression,and p-AMPK,SIRT1,and PGC-1α protein expression were increased(P＜0.05,P＜0.01).Compared with the Wendan Decoction group,the Modified Wendan Decoction group showed higher myocardial ATP content and PGC-1α protein expression(P＜0.05,P＜0.01).Conclusions Modified Wendan Decoction effectively mitigated myocardial injury,lowered blood lipid levels,regulated myocardial energy metabolism,and alleviated oxidative stress in rats,with its underlying mechanism potentially linked to the modulation of the AMPK/SIRT1/PGC-1α signaling pathway.