基于网络药理学、分子对接及实验验证探讨益气通痹胶囊对缺血性心力衰竭干预机制  

Exploration on the Intervention Mechanism of Yiqi Tongbi Capsules in Ischemic Heart Failure Based on Network Pharmacology,Molecular Docking and Experimental Verification

作　　者：李中政 李滨[1] 郭文辉 郭进建[1] LI Zhongzheng;LI Bin;GUO Wenhui;GUO Jinjian(The Second People’s Hospital Affiliated to Fujian University of Chinese Medicine,Fuzhou 350003,China)

机构地区：[1]福建中医药大学附属第二人民医院,福建福州350003

出　　处：《中国中医药信息杂志》2025年第4期42-50,共9页Chinese Journal of Information on Traditional Chinese Medicine

基　　金：福建省自然科学基金面上项目(2024J01736);福建中医药大学校管科研课题临床专项(XB2024031);福建中医药大学重大科技创新“揭榜挂帅”专项项目(XJB2022003-1)。

摘　　要：目的运用网络药理学方法和分子对接技术探讨益气通痹胶囊治疗缺血性心力衰竭(IHF)的作用机制,并通过体内实验进行验证。方法利用TCMSP、BATMAN-TCM数据库筛选益气通痹胶囊的活性成分及其对应靶点。利用GeneCards、OMIM、TTD数据库检索IHF疾病相关靶点。对药物活性成分靶点与IHF疾病相关靶点取交集,得到共同靶点,构建中药-活性成分-共同靶点网络,筛选益气通痹胶囊治疗IHF的关键活性成分。将共同靶点导入STRING数据库,获取蛋白相互作用(PPI)网络,并筛选核心靶点。运用Metascape平台对共同靶点进行GO及KEGG通路富集分析。将关键活性成分与核心靶点通过AutoDock4.2.6软件进行分子对接。采用手术结扎左前降支冠状动脉法构建IHF小鼠模型,将小鼠随机分为假手术组、模型组、卡托普利组(3.25 mg/kg)及益气通痹胶囊低、中、高剂量组(2.34、4.68、9.36 g/kg),连续给药6周,使用多普勒超声成像系统检测小鼠心功能,RT-qPCR检测小鼠心肌组织微管相关蛋白轻链3B(LC3B)、自噬效应蛋白1(Beclin1)、自噬降解底物(p62)、表皮生长因子受体(EGFR)、信号转导和转录激活因子3(STAT3)mRNA表达。结果共筛选出益气通痹胶囊治疗IHF的潜在作用靶点186个,前5个关键活性成分为槲皮素、β-谷甾醇、木犀草素、豆甾醇、黄芩素,较为关键的核心靶点包括AKT1、STAT3、HIF1A、BCL2、EGFR等,核心靶点主要参与活性氧代谢过程、细胞因子受体结合等,涉及脂质和动脉粥样硬化、AGE-RAGE信号通路、IL-17信号通路等通路。关键活性成分与核心靶点均具有较好的结合亲和力。益气通痹胶囊可显著改善IHF小鼠心功能,RT-qPCR结果显示模型组小鼠心肌组织EGFR/STAT3信号通路和自噬过程被激活但不足以改善IHF,而益气通痹胶囊能显著上调小鼠心肌组织LC3B、Beclin1 mRNA表达,下调p62、EGFR、STAT3 mRNA表达。结论益气通痹胶囊可能通过调Objective To explore the mechanism of Yiqi Tongbi Capsules in the treatment of ischemic heart failure(IHF)using network pharmacological method and molecular docking technique;To verify through in vivo experiments.Methods The effective components and corresponding target of Yiqi Tongbi Capsules were screened using TCMSP and BATMAN-TCM databases.The targets related to IHF disease were searched using GeneCards,OMIM and TTD databases.The common targets between the drug active components and IHF disease-related targets were obtained.A Chinese materia medica-active component-common target network was constructed to select the key targets.The common targets were input into the STRING database to obtain PPI network relationships,and the core targets were selected.The GO function and KEGG pathway enrichment analyses were performed on the common targets using the Metascape platform.The key active components and core targets were verified by molecular docking using the AutoDock 4.2.6 software.A mouse IHF model was established by ligating the left anterior descending branch of the coronary artery surgically,and the mice were divided into sham-operation group,model group,captopil group(3.25 mg/kg),Yiqi Tongbi Capsules low-,medium-,and high-dosage groups(2.34,4.68,9.36 g/kg).The heart function of mice was detected by Doppler ultrasound imaging system for 6 weeks after continuous administration;the mRNA expressions of LC3B,Beclin1,p62,EGFR and STAT3 were detected by RT-qPCR in mouse myocardial tissue.Results A total of 186 potential target genes for the therapeutic effects of Yiqi Tongbi Capsules on IHF were screened out;the top 5 key active components were quercetin,β-sitosterol,lutein,stigmasterol and baicalein;the core targets included AKT1,STAT3,HIF1A,BCL2 and EGFR,etc.The GO function and KEGG enrichment analysis showed that the core targets mainly participated in the processes of active oxygen metabolism,cytokine receptor binding,and involving the pathways of lipid and atherosclerosis,AGE-RAGE signaling pathway and IL-17

关 键 词：益气通痹胶囊 缺血性心力衰竭 网络药理学 分子对接 自噬 

分 类 号：R285[医药卫生—中药学]