芪参颗粒中獐牙菜苷对过量异丙肾上腺素致小鼠心力衰竭的保护作用

Protective effect of sweroside on heart failure induced by excessive isoproterenol in mice

关键词:  獐牙菜苷  心力衰竭  Na⁺-K⁺-ATP酶α1亚基  能量代谢

Key words:  sweroside  heart failure  ATPase Na⁺/K⁺ Transporting Subunit Alpha 1  energy metabolism

摘要:

[目的]心力衰竭（简称心衰）是许多心血管疾病的终末阶段。芪参颗粒治疗心衰疗效确切，獐牙菜苷可能是其主要活性成分之一。本研究旨在评价獐牙菜苷对异丙肾上腺素（ISO）诱导的小鼠心衰的保护作用，并初步探讨其作用靶点与机制。[方法]通过皮下注射过量ISO构建心衰小鼠模型，随机分为空白组、模型组、卡托普利组、獐牙菜苷组。超声心动评价心功能、苏木精-伊红（HE）染色法检测心肌病理变化、BATMAN-TCM数据库预测作用靶点，蛋白免疫印迹（Western blot）法检测靶点蛋白表达水平。[结果]与空白组相比，模型组小鼠射血分数（EF）、短轴缩短率（FS）显著降低（P<0.01），左室收缩末内径（LVIDs）显著增大（P<0.01）。同模型组比，獐牙菜苷组小鼠EF值、FS值增加，LVIDs值降低（P<0.01）。组织病理学检查可见模型组小鼠心脏左心室壁变薄、心肌纤维变细，局部心肌纤维坏死，或伴炎细胞浸润等，獐牙菜苷组心肌细胞形态较为正常。BATMAN-TCM数据库提示，钠钾ATP酶α1亚基（ATP1A1）是獐牙菜苷治疗心衰的靶标。Western blot结果显示，模型组ATP1A1蛋白表达下调，獐牙菜苷可增加ATP1A1蛋白含量。[结论]本研究通过基础药理学与网络药理学相结合的研究方法，证明了獐牙菜苷能显著改善ISO诱导的小鼠心衰，初步证明其机制可能与增加ATP1A1蛋白表达，改善心肌能量代谢有关。

Abstract:

Heart failure is the serious end-stage of many cardiovascular diseases. Qishen granule has a definite therapeutic effect on heart failure,and the sweroside may be one of the active ingredients to exert its pharmacodynamic effect. The aim of this study was to evaluate the protective effect of sweroside on heart failure induced by excessive isoproterenol in mice,and to explore its potential target and mechanism. Heart failure mice model was established by subcutaneous injection of excessive isoprenaline. Mice were randomly divided into four groups,including control group,model group,sweroside group and captopril group. Cardiac function was evaluated by echocardiography,myocardial pathological changes were detected by HE staining,drug targets were predicted by BATMAN-TCM database,and protein expression of the potential target was detected by Western blot. Compared with the control group,EF and FS of mice in the model group were significantly decreased (P<0.01),while LVIDs was significantly increased (P<0.01). EF and FS were increased in mice treated by sweroside,and LVIDs were decreased (P<0.01). In Histopathological examination,thinned left ventricular wall,thinned myocardial fiber, scattered necrosis of myocardial cells,as well as aggregation of inflammatory cells were found in model mice. The morphology of myocardial tissue were obtained approximate normal by sweroside. BATMAN-TCM analysis showed that ATP1A1 is the candidate target of sweroside in heart failure. Western blot results showed that the expression of ATP1A1 was rescued by sweroside. In this study,by combining of basic pharmacology and network pharmacology, we reported that sweroside significantly improved ISO-induced heart failure in mice through increasing ATP1A1 and then improving myocardial energy metabolism.