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OA
Mechanism of Shenyu Yangxin Capsules in Ameliorating Myocardial Fibrosis in Chronic Heart Failure Mice by Activating the Hippo-YAP Pathway
目的 探讨参萸养心胶囊(SY)通过激活Hippo-YAP(河马-Yes相关蛋白)通路对慢性心力衰竭小鼠心肌纤维化的改善机制.方法 60 只小鼠随机分为正常组、模型组、参萸养心胶囊低剂量组、参萸养心胶囊高剂量组、福辛普利钠组 5 个组,采用注射盐酸异丙肾上腺素(ISO)复制慢性心力衰竭动物模型.给药组以不同剂量参萸养心胶囊和福辛普利钠干预慢性心力衰竭模型小鼠,通过心功能检测、HE和Masson染色检测小鼠心脏组织病理结构和心肌纤维化水平;ELISA法测定血清脑钠肽(BNP)、白细胞介素 6(IL-6)水平;免疫荧光法测定小鼠心肌组织中心肌纤维化和YAP相关因子Ⅰ型胶原蛋白(Col-Ⅰ)、Ⅲ型胶原蛋白(Col-Ⅲ)、磷酸化Yes相关蛋白(p-YAP)和磷酸化大肿瘤抑制激酶 1(p-LATS1)的表达;TUNEL染色法测定小鼠心肌组织中心肌细胞死亡率;RT-qPCR 法检测小鼠心肌组织 YAP、LATS1、Col-Ⅰ、Col-Ⅲ、α-平滑肌肌动蛋白(α-SMA)和GAPDH mRNA的表达;Western Blot法检测小鼠心肌组织Hippo-YAP信号通路以及与心肌纤维化相关蛋白的表达.结果 与正常组小鼠比较,模型组小鼠左室射血分数(LVEF)和左室短轴缩短率(LVFS)降低,左室舒张末期内径(LVEDD)、左室收缩末期内径(LVESD)、血清BNP和IL-6 均升高(P＜0.01);与模型组比较,参萸养心胶囊给药组和福辛普利钠组小鼠LVEF和LVFS升高,LVEDD、LVESD、BNP和IL-6 均降低(P＜0.05,P＜0.01).与正常组小鼠比较,模型组小鼠中Col-Ⅰ、Col-Ⅲ、YAP、LATS1 和α-SMA的蛋白与mRNA表达均升高(P＜0.01);与模型组比较,参萸养心胶囊给药组和福辛普利钠组中的Col-Ⅰ、Col-Ⅲ、YAP、LATS1和α-SMA的蛋白与mRNA表达均降低(P＜0.05,P＜0.01).结论 参萸养心胶囊可能通过激活Hippo-YAP通路来发挥对慢性心力衰竭小鼠心肌纤维化的保护作用.
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.
兰琪;伍浩;李小林;罗钢;宋梦林;薛进宜;刘孟楠
西南医科大学中西医结合学院/附属中医医院,四川 泸州 646000西南医科大学中西医结合学院/附属中医医院,四川 泸州 646000西南医科大学中西医结合学院/附属中医医院,四川 泸州 646000西南医科大学中西医结合学院/附属中医医院,四川 泸州 646000西南医科大学中西医结合学院/附属中医医院,四川 泸州 646000西南医科大学中西医结合学院/附属中医医院,四川 泸州 646000西南医科大学中西医结合学院/附属中医医院,四川 泸州 646000
医药卫生
参萸养心胶囊慢性心力衰竭心肌纤维化Hippo-YAP通路小鼠
Shenyu Yangxin Capsuleschronic heart failuremyocardial fibrosisHippo-YAP pathwaymice
《中药新药与临床药理》 2026 (8)
1454-1463,10
国家自然科学基金面上项目(82074378)四川省科技厅项目(2026NSFSC1823)四川省医学会青年创新项目(Q20250014)西南医科大学项目(2024ZXYZX30).
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