基于网络药理学、分子对接和实验验证探讨五参汤治疗慢性心力衰竭的作用机制  

Study on the Mechanism of Wushen Decoction in the Treatment of Chronic Heart Failure Based on Network Pharmacology,Molecular Docking and Experimental Verification

作　　者：王继儒 杨桦[3] 殷春霞 蓝涛华[3] 吕渭辉 张燕[1,3] WANG Jiru;YANG Hua;YIN Chunxia;LAN Taohua;LYU Weihui;ZHANG Yan(The Second Clinical Medical School of Guangzhou University of Chinese Medicine,Guangzhou 510020 Guangdong,China;Guangdong Provincial Laboratory of Traditional Chinese Medicine,Guangzhou 510020 Guangdong,China;Guangdong Provincial Hospital of Chinese Medicine,Guangzhou 510020 Guangdong,China;State Key Laboratory of Traditional Chinese Medicine Syndrome,Guangzhou 510020 Guangdong,China)

机构地区：[1]广州中医药大学第二临床医学院,广东广州510020 [2]中医药广东省实验室,广东广州510020 [3]广东省中医院,广东广州510020 [4]中医证候全国重点实验室,广东广州510020

出　　处：《中药新药与临床药理》2025年第3期392-404,共13页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：国家自然科学基金面上项目(82074369)。

摘　　要：目的基于网络药理学、分子对接和动物实验验证探讨五参汤治疗慢性心力衰竭(CHF)的作用机制。方法利用TCMSP数据库获取五参汤药物中的活性成分。通过SwissTargetPrediction平台及OMIM、TTD、DisGeNet、GeneCards数据库得到五参汤成分及慢性心力衰竭的基因靶点,二者交集靶点为五参汤治疗慢性心力衰竭的潜在靶点。由Cytoscape数据库得到核心靶点,将核心靶点再次计算后筛选得到重要靶点,并构建“药物-成分-核心靶点”网络及靶点蛋白互作网络(PPI)。以重要靶点在R软件上进行GO及KEGG富集分析。随后采用分子对接验证主要活性成分与关键通路的靶点的结合水平,并在此基础上进行实验验证。采用小鼠心肌梗死致慢性心力衰竭模型,利用B超、HE、Masson及Western Blot验证实验结果。结果共收集到有效药物成分63种,成分相关靶点768个和疾病靶点12933个,二者交集共706个靶点。在Cytoscape中计算得到核心靶点137个,其中重要靶点为28个。PPI提示STAT3、Caspase-3、Bcl2为治疗过程的关键靶点。GO及KEGG分析显示五参汤治疗慢性心力衰竭可能通过小分子代谢、激素反应、碳水化合物代谢和氧化应激反应来实现,这些进程可能与AGE-RAGE信号通路、PI3K-Akt信号通路、IL-17信号通路以及HIF-1通路有关。B超、HE、MASSON结果示,与模型组相比,给药组不同程度地缓解了小鼠的心功能障碍及炎症浸润和纤维化等病理改变。Western Blot结果显示五参汤能逆转STAT3、HIF1A、Caspase-3的高表达(P<0.05,P<0.01,P<0.001)以及Bcl2的低表达(P<0.05),从而使慢性心力衰竭得到改善。结论五参汤可能通过抑制HIF1A、STAT3、Caspase-3的蛋白表达,同时增加Bcl2的蛋白表达,实现对HIF-1通路及凋亡相关信号的调控发挥对慢性心力衰竭的治疗作用。Objective To explore the mechanism of Wushen Decoction in the treatment of chronic heart failure(CHF)based on network pharmacology,molecular docking and animal experiments.Methods The active components in Wushen Decoction were obtained by TCMSP database.The SwissTargetPrediction platform and OMIM,TTD,DisGeNet,GeneCards databases were used to obtain the components of Wushen Decoction and the gene targets of chronic heart failure.The intersection of the two targets was the potential target of Wushen Decoction in the treatment of CHF.The core targets were obtained by Cytoscape,among which the important targets were calculated again,and the‘drugs-components-core targets’network and target PPI were constructed.GO and KEGG enrichment analysis was performed on R with important targets.Subsequently,molecular docking was used to verify the binding level of the main active components to the targets of the key pathways,and experimental verification was performed on this basis.The CHF model induced by myocardial infarction in mice was used to verify the experimental results by B-ultrasound,HE,Masson and Western Blot.Results A total of 63 effective drug components were collected.There were 768 componentrelated targets and 12933 disease targets,with a total of 706 targets.A total of 137 core targets were calculated in Cytoscape,of which 28 were important targets.PPI suggested that STAT3,Caspase-3 and Bcl2 were the key targets in the treatment process.GO and KEGG analysis showed that the treatment of chronic heart failure with Wushen Decoction may be achieved through small molecule metabolism,hormone response,carbohydrate metabolism and oxidative stress response.These processes may be related to AGE-RAGE signaling pathway,PI3K-Akt signaling pathway,IL-17 signaling pathway and HIF-1 pathway.The results of B-ultrasound,HE and MASSON showed that compared with the model group,the administration group alleviated the pathological changes of cardiac dysfunction,inflammatory infiltration and fibrosis in mice to varying degrees.West

关 键 词：五参汤 慢性心力衰竭 网络药理学 分子对接 实验验证 小鼠 

分 类 号：R285.5[医药卫生—中药学]