人参总次苷调控PGC1α信号通路改善心梗后大鼠心肌能量代谢OA

Objective:To investigate the effect of total secondary ginsenosides on improving myocardial energy me-tabolism in post-myocardial infarction rats by regulating peroxisome proliferator-activated receptor-gamma coactivator 1α(PGC1α)signaling pathway and explore its underlying mechanism.Methods:A total of 100 SD rats were selected and underwent ligation of the anterior descending branch of the left coronary artery to establish a myocardial infarction model.The rats were randomly divided into five groups:normal control group,model control group,groups receiving total second-ary ginsenosides at doses of 11.6 and 23.3 mg/kg(TSG-L and TSG-H groups),and coenzyme Q10 group(10 mg/kg).Each group was given the corresponding drugs by gavage for four weeks.Myocardial tissue injury was observed by hema-toxylin-eosin(HE)staining and Masson's trichrome staining.The contents of hydroxyproline(HYP),adenosine triphosphate(ATP),adenosine diphosphate(ADP),and adenosine monophosphate(AMP)in the myocardium were de-tected using colorimetric assay kits.The mitochondrial membrane potential of the myocardium was detected by flow cy-tometry.The mRNA expression levels of mitochondrial transcription factor A(Tfam),PGC1α,estrogen-related receptor α(Errα),nuclear respiratory factor 1(Nrf1),nuclear respiratory factor 2(Nrf2),and peroxisome proliferator-activated receptor alpha(Pparα)in myocardium were detected by real-time PCR(RT-PCR).Protein expression levels of Na+-K+-ATPase,uncoupling protein 2(UCP2),adenine nucleotide translocator(ANT),TFAM,PGC-1α,ERRα,NRF-1,NRF-2,and PPARα were detected by Western Blot.Results:Compared with that in the normal control group,the myo-cardial tissue damage in the model control group was significantly aggravated,while collagen volume fraction and HYP content were increased significantly(P<0.01),accompanied by significantly decreased ATP content and markedly in-creased ADP and AMP levels(P<0.01).The protein expression of ANT and Na+-K+-ATPase was downregulated,while that of UCP2 was upregulated(P<0.01).The mitochondrial membrane potential of the myocardium was significantly re-duced,and both protein and mRNA expression levels of TFAM,PGC-1α,ERRα,NRF-1,NRF-2,and PPARα were signif-icantly downregulated(P<0.01).Compared with the model control group,groups treated with total secondary ginsen-osides(11.65 and 23.3 mg/kg)and coenzyme Q10(10 mg/kg)exhibited significantly alleviated myocardial tissue damage,markedly reduced collagen volume fraction and HYP content(P<0.01),significantly increased ATP levels,and markedly decreased ADP and AMP levels(P<0.01).In the TSG-L group,the protein expression of ANT was upregulat-ed,while that of UCP2 was downregulated(P<0.01).The mitochondrial membrane potential and TFAM protein levels were significantly increased(P<0.01),and the protein and mRNA expression levels of PGC1α,ERRα,NRF1,NRF2,and PPARα were significantly upregulated(P<0.05 or P<0.01).In the TSG-H and coenzyme Q10 groups,protein ex-pression levels of Na+-K+-ATPase and ANT were upregulated,while UCP2 protein expression was downregulated(P<0.01).Additionally,significant increases were observed in mitochondrial membrane potential and in the protein and mR-NA expression levels of TFAM,PGC1α,ERRα,NRF1,NRF2,and PPARα(P<0.01).Conclusion:Total secondary ginsenosides can improve myocardial injury after myocardial infarction,balance myocardial high-energy phosphate metab-olism and related transporter protein expression,and elevate myocardial mitochondrial membrane potential,thereby impro-ving myocardial energy metabolism.Its mechanism may be related to upregulating the expression of PGC1α signaling pathway-related factors.