中药新药与临床药理2025，Vol.36Issue(11)：1819-1828,10.DOI:10.19378/j.issn.1003-9783.2025.11.001
暖心康通过支链氨基酸代谢促进心肌细胞自噬改善心力衰竭小鼠的心功能
Nuanxinkang Improves Cardiac Function in Heart Failure Mice by Promoting Branched-Chain Amino Acid Metabolism to Enhance Cardiomyocyte Autophagy
摘要
Abstract
Objective To investigate the mechanism by which Nuanxinkang regulates branched-chain amino acid(BCAA)metabolism to improve pressure overload-induced heart failure in mice.Methods A pressure overload-induced heart failure mouse model was established using transverse aortic constriction(TAC).C57BL/6J mice were randomly divided into sham-operated group,model group,Nuanxinkang group,Nuanxinkang+3-MA group,and Entresto group,with 8 mice per group.The Nuanxinkang group received 1.65 g·kg-1 of Nuanxinkang via gavage daily for 6 weeks.The Entresto group received 25 mg·kg-1 of Entresto via gavage daily.The Nuanxinkang+3-MA group received the same Nuanxinkang intervention with additional intraperitoneal injection of 10 mg·kg-1 of the autophagy inhibitor 3-methyladenine(3-MA)daily during the fourth week for 1 week.Cardiac function was assessed using echocardiography:left ventricular ejection fraction(LVEF),left ventricular fractional shortening(LVFS),left ventricular internal diameter at end-diastole(LVIDd),and left ventricular internal diameter at end-systole(LVIDs).Pathological changes in myocardial tissue were observed using hematoxylin-eosin(HE)and wheat germ agglutinin(WGA)staining.Immunofluorescence was used to detect LC3B protein expression in cardiomyocytes.qPCR was employed to measure mRNA expression levels of ANP and BNP in myocardial tissue.ELISA was used to detect BCAA levels in myocardial tissue.Western Blot was performed to assess protein expression of BCKDK,p-E1α,E1α,p-mTOR,mTOR,LC3,and P62 in myocardial tissue.Results(1)Compared with the sham-operated group,the model group showed significantly decreased LVEF and LVFS(P＜0.01),significantly increased LVIDd and LVIDs(P＜0.01),markedly enlarged cardiomyocytes with disordered arrangement and increased inflammatory cell infiltration,significantly increased cardiomyocyte cross-sectional area(P＜0.01),significantly upregulated ANP and BNP mRNA expression in myocardial tissue(P＜0.01),significantly downregulated LC3B protein expression in cardiomyocytes(P＜0.01),significantly upregulated p-mTOR/mTOR and P62 protein expression(P＜0.01),significantly downregulated LC3 II/I protein expression(P＜0.01),significantly increased BCAA content in myocardial tissue(P＜0.01),and significantly upregulated BCKDK and p-E1α/E1α protein expression(P＜0.01).(2)Compared with the model group,the Nuanxinkang group showed significantly increased LVEF and LVFS(P＜0.01),significantly decreased LVIDd and LVIDs(P＜0.05,P＜0.01),improved cardiomyocyte pathological morphology with ordered arrangement and reduced inflammatory cell infiltration,significantly reduced cardiomyocyte size and cross-sectional area(P＜0.01),significantly downregulated mRNA expression of ANP and BNP(P＜0.01),significantly upregulated LC3B protein expression(P＜0.01),significantly downregulated protein expression of p-mTOR/mTOR and P62(P＜0.01),significantly upregulated LC3 II/I protein expression(P＜0.05),significantly decreased BCAA content in myocardial tissue(P＜0.01),and significantly downregulated protein expression of BCKDK and p-E1α/E1α(P＜0.01).(3)Compared with the Nuanxinkang group,the Nuanxinkang+3-MA group showed significantly decreased LVEF and LVFS(P＜0.01),significantly increased LVIDd and LVIDs(P＜0.05),disordered cardiomyocyte arrangement with increased inflammatory cell infiltration,significantly increased cardiomyocyte size and cross-sectional area(P＜0.01),significantly upregulated mRNA expression of ANP and BNP(P＜0.01),significantly downregulated LC3B protein expression(P＜0.01),significantly upregulated protein expression of p-mTOR/mTOR and P62(P＜0.01),significantly downregulated LC3 Ⅱ/Ⅰ protein expression(P＜0.05),significantly increased BCAA content in myocardial tissue(P＜0.05),and significantly upregulated protein expression of BCKDK and p-E1α/E1α(P＜0.05).Conclusion Nuanxinkang effectively improves cardiac function in heart failure mice,potentially by promoting BCAA metabolism and enhancing cardiomyocyte autophagy.关键词
暖心康/心力衰竭/支链氨基酸/mTOR/心肌细胞/自噬/小鼠Key words
Nuanxinkang/heart failure/branched-chain amino acids/mTOR/cardiomyocyte/autophagy/mice分类
医药卫生引用本文复制引用
庞淑瑾,陈瑞雪,陈鑫,郭依宁,张钰冰,庄皓文,梁碧容,王陵军..暖心康通过支链氨基酸代谢促进心肌细胞自噬改善心力衰竭小鼠的心功能[J].中药新药与临床药理,2025,36(11):1819-1828,10.基金项目
国家自然科学基金项目(82474403) （82474403）
广东省自然科学基金面上项目(2024A1515012171) （2024A1515012171）
广东省基础与应用基础研究基金联合基金项目(2023A1515110747) （2023A1515110747）
广州市科技计划项目(2024A03J0348) （2024A03J0348）
东莞市社会发展科技项目高水平医院建设专项(20231800923372) （20231800923372）
国家中医药传承创新中心项目(2023QN19). （2023QN19）
