The Effect Of Qiliqiangxin On Attenuating Ventricular Remodeling After Myocardial Infarction In Estrogen-deficiency Mice And The Underlying Mechanism

Objective:Acute myocardial infarction(AMI)has been a world-wide disease due to its high morbidity and mortality.Post-menopausal women are more likely to affect AMI and has a poorer prognosis compared to the pre-menopausal women and the age-matched men because of the lack of estrogen.A multi-center,randomized,paralleled,double-blind study published by our group established that a Chinese medication named Qiliqiangxin(QLQX)has a treatment effect on patients suffering chronic heart failure.This study was designed to investigate the therapeutic effect of Chinese medication QLQX on adverse cardiac remodeling after myocardial infarction(MI)in bilateral ovariectomized(OVX)female mice and the molecular mechanism underlying ths effect.Methods:Eight-week old female C57BL/6 mice were operated to ligate the left anterior descending coronary artery seven days after bilateral ovariectomy and were orally administered either QLQX or vehicle(0.5g/kg/d).21 days after ligation,echocardiography was performed to evaluate the heart function of all the mice.Masson's Trichrome staining was applied to evaluate myocardial fibrosis.Collagen deposition was determined by the mRNA level of Collagen ?,Collagen ? and?-SMA using real-time quantitative polymerase chain reaction(qPCR).Myocardial apoptosis was examined by TUNEL staining and western blotting analysis was used to detect the molecular pathways.In the further study after PPAR? was found to be up-regulated by QLQX.Rosiglitazone or T0070907 was injected to the mice to activate or inhibit PPAR? to see whether activation or inhibition of PPAR? would further promote or abolish the protective effect of QLQX and whether PPAR? was necessary for the protective effect of QLQX.Furthermore,genes involved in cardiac energy metabolism were detected by real time qPCR to observe the effect of OVX,MI and QLQX on cardiac energy metabolism.Results:These mice displayed a significant reduction in heart function,increased myocardial fibrosis and apoptosis,and decreased expression of peroxisome proliferator activated receptor ?(PPAR?)in the heart tissue,which could be reversed by QLQX treatment.Inhibition of PPAR? reduced QLQX-mediated cardio-protective effects,while PPAR? activation did not further enhance the beneficial effect of QLQX.Furthermore,QLQX upregulated 9 genes(Cd36,Fatp,Pdk4,Acadm,Acad1,Acadv1,Cpt1a,Cpt1b and Cpt2),facilitating energy metabolism of the OVX/MI hearts and 5(Acadm,Acadl,Cpt1a,Cpt1b,Cpt2)of the 9 genes were the downstream targets of PPAR?.Conclusions:The present study indicates that QLQX has a treatment effect on pathological remodeling post MI in bilateral OVX female mice via activation of PPAR?,suggesting that QLQX may be a promising prescription for the treatment of postmenopausal women suffering from MI.