Mechanism of Qifu Qiangxin Decoction Relieving Myocardial Damage in Heart Failure Mice with Heart-Kidney Yang Defi-ciency Syndrome / 浙江中医药大学学报

ABSTRACT

[Objective]To explore the mechanism of Qifu Qiangxin Decoction mitigating myocardial damage in heart failure(HF)mice with heart-kidney Yang deficiency syndrome.[Methods]Thirty C57BL/6 mice were randomly divided into Sham surgery group(Sham group),HF model(HF)group,low-dose Qifu Qiangxin Decoction(HF+QL)group,high-dose Qifu Qiangxin Decoction(HF+QH)group and western medicine[HF+angiotensin converting enzyme inhibitors(ACEI)]group,six in each group.In Sham group,the skin was cut open after anesthesia,the heart was exposed,the left anterior descending coronary artery was not in ligation,and then sutured.The rest were used to establish a mouse model of HF with heart-kidney Yang deficiency syndrome after myocardial infarction(MI)by ligating the left anterior descending coronary artery and swimming in cold water,then treated for 15 days.After treatment,the state of the mice was recorded,left ventricular end-diastolic volume(LVEDV),left ventricular end-systolic volume(LVESV),ejection fraction(EF)and left ventricular fractional shortening(LVFS)were measured by echocardiography to evaluate cardiac function;hematoxylin-eosin(HE)staining was used to evaluate the morphological of myocardial tissue;the serum levels of B-syndrome natriuretic peptide(BNP)were measured by enzyme linked immunosorbent assay(ELISA);terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL)was used to detect cardiomyocyte apoptosis;Western blot was used to determine the expression levels of apoptosis related proteins,autophagy related proteins and adenosine monophosphate-activated protein kinase/mammalian target of rapamycin(AMPK/mTOR)signaling pathway related proteins in mice myocardial tissue.[Results]Qifu Qiangxin Decoction can relieve the symptoms of HF in mice.Compared with Sham group,EF and LVFS values of mice in HF group were significantly decreased,while LVEDV and LVESV were significantly increased(P＜0.01).Compared with HF group,EF and LVFS values in each group were significantly increased,while LVEDV and LVESV were significantly decreased(P＜0.01),moreover,HF+QH group had a better effect than that of HF+QL group.According to HE staining,extensive necrotic myocardial tissue was observed in HF group compared with Sham group,and ELISA showed a significant increase in BNP levels(P＜0.01).Compared with HF group,the pathological conditions of myocardial tissue were relieve in each group,and the level of BNP was also significantly reduced(P＜0.01).TUNEL staining and Western blot results showed that the level of apoptosis in HF group was significantly increased compared with Sham group(P＜0.05).Compared with HF group,the apoptosis level of the each group was significantly reduced(P＜0.05).Therefore,Qifu Qiangxin Decoction could significantly reduce the level of cardiomyocyte apoptosis.Western blot detection of autophagy-related proteins and AMPK/mTOR signaling pathway related proteins showed that Qifu Qiangxin Decoction could significantly enhance autophagy level and regulate AMPK/mTOR signaling pathway in a concentration-dependent manner.[Conclusion]Qifu Qiangxin Decoction can regulate AMPK/mTOR signaling pathway,inhibit cell apoptosis and induce autophagy,thus protecting cardiomyocytes and mitigating myocardial injury.