Qiliqiangxin Attenuates Adverse Cardiac Remodeling after Myocardial Infarction in Ovariectomized Mice via Activation of PPAR?3

摘要

>Background/Aims: This study was designed to investigate the therapeutic effect of traditional Chinese medication Qiliqiangxin (QLQX) on adverse cardiac remodeling after myocardial infarction (MI) in bilateral ovariectomized (OVX) female mice. 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. 21 days after ligation, echocardiography was performed to evaluate the heart function of all mice. Masson's Trichrome staining was applied to evaluate myocardial fibrosis. Collagen deposition was determined by the mRNA level of Collagen I, Collagen III and ?±-SMA using real-time quantitative polymerase chain reaction (qPCR). Myocardial apoptosis was examined by the protein level of Bax, Bcl2 and the Bcl2/Bax ratio using western blotting. Results: These mice displayed a significant reduction in heart function, increased myocardial fibrosis and apoptosis, and decreased expression of peroxisome proliferator activated receptor ?3 (PPAR?3) in the heart tissue, which could be reversed by QLQX treatment. Inhibition of PPAR reduced QLQX-mediated cardio-protective effects, while PPAR?3 activation did not further enhance the beneficial effect of QLQX. Furthermore, QLQX upregulated 9 genes (Cd36, Fatp, Pdk4, Acadm, Acadl, Acadvl, Cpt1a, Cpt1b and Cpt2) facilitating energy metabolism in the MI hearts of the OVX mice and 5 (Acadm, Acadl, Cpt1a, Cpt1b, Cpt2) of the 9 genes were the downstream targets of PPAR?3. Conclusion: The present study indicates that QLQX has a treatment effect on pathological remodeling post MI in bilateral OVX female mice via activation of PPAR?3, suggesting that QLQX may be a promising prescription for the treatment of postmenopausal women suffering from MI.