中药新药与临床药理2026，Vol.37Issue(8)：1454-1463,10.DOI:10.19378/j.issn.1003-9783.2026.08.007
参萸养心胶囊通过激活Hippo-YAP通路改善慢性心力衰竭小鼠心肌纤维化的机制
Mechanism of Shenyu Yangxin Capsules in Ameliorating Myocardial Fibrosis in Chronic Heart Failure Mice by Activating the Hippo-YAP Pathway
摘要
Abstract
Objective To investigate the mechanism by which Shenyu Yangxin Capsules(SY)ameliorates myocardial fibrosis in chronic heart failure(CHF)mice through activating the Hippo-YAP pathway.Methods Sixty mice were randomly divided into five groups:normal group,model group,SY low-dose group,SY high-dose group,and fosinopril sodium group.The animal model was established by injection of isoproterenol hydrochloride(ISO).The treatment groups were intervened with different doses of SY or fosinopril sodium.Cardiac function was assessed,and the pathological structure and myocardial fibrosis level were evaluated by HE and Masson staining.Serum levels of brain natriuretic peptide(BNP)and interleukin-6(IL-6)were measured by ELISA.Immunofluorescence was used to detect the expression of myocardial fibrosis and YAP related factors,including collagen type Ⅰ(Col-Ⅰ),collagen type Ⅲ(Col-Ⅲ),phosphorylated Yes-associated protein(p-YAP),and phosphorylated large tumor suppressor kinase 1(p-LATS1).Cardiomyocyte apoptosis was detected by TUNEL staining.The mRNA expression of YAP,LATS1,Col-Ⅰ,Col-Ⅲ,α-smooth muscle actin(α-SMA),and GAPDH was detected by RT-qPCR.The protein expression of Hippo-YAP signaling pathway and myocardial fibrosis-related proteins was detected by Western Blot.Results Compared with the normal group,the model group showed decreased left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS),and increased left ventricular enddiastolic dimension(LVEDD),left ventricular endsystolic dimension(LVESD),BNP,and IL-6 levels(P<0.01).Compared with the model group,the SY treatment groups and the fosinopril sodium group showed increased LVEF and LVFS,and decreased LVEDD,LVESD,BNP,and IL-6 levels(P<0.05,P<0.01).Compared with the normal group,the model group showed increased protein and mRNA expression of Col-Ⅰ,Col-Ⅲ,YAP,LATS1,and α-SMA(P<0.01).Compared with the model group,the SY treatment groups and the fosinopril sodium group showed decreased protein and mRNA expression of Col-Ⅰ,Col-Ⅲ,YAP,LATS1,and α-SMA(P<0.05,P<0.01).Conclusion Shenyu Yangxin Capsules may exert a protective effect against myocardial fibrosis in chronic heart failure mice by activating the Hippo-YAP pathway.关键词
参萸养心胶囊/慢性心力衰竭/心肌纤维化/Hippo-YAP通路/小鼠Key words
Shenyu Yangxin Capsules/chronic heart failure/myocardial fibrosis/Hippo-YAP pathway/mice分类
医药卫生引用本文复制引用
兰琪,伍浩,李小林,罗钢,宋梦林,薛进宜,刘孟楠..参萸养心胶囊通过激活Hippo-YAP通路改善慢性心力衰竭小鼠心肌纤维化的机制[J].中药新药与临床药理,2026,37(8):1454-1463,10.基金项目
国家自然科学基金面上项目(82074378) （82074378）
四川省科技厅项目(2026NSFSC1823) （2026NSFSC1823）
四川省医学会青年创新项目(Q20250014) （Q20250014）
西南医科大学项目(2024ZXYZX30). （2024ZXYZX30）
