基于网络药理学与分子对接探究四妙勇安汤调控巨噬细胞改善心肌缺血再灌注损伤的机制  

Exploration on molecular mechanism of Simiao Yong’an Decoction regulating macrophages to improve myocardial ischemia-reperfusion injury based on network pharmacology and molecular docking

作　　者：李思可 乔柏维 刘士嘉 袁海宁 谢盈彧 LI Sike;QIAO Baiwei;LIU Shijia;YUAN Haining;XIE Yingyu(College of Traditional Chinese Medicine,Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China)

机构地区：[1]天津中医药大学中医学院,301617 [2]天津市现代中医理论创新转化重点实验室 [3]山东中医药大学第一临床医学院

出　　处：《环球中医药》2025年第3期468-482,共15页Global Traditional Chinese Medicine

基　　金：国家自然科学基金青年项目(82104721)。

摘　　要：目的基于网络药理学和分子对接技术研究四妙勇安汤通过调控巨噬细胞改善心肌缺血再灌注损伤(myocardial ischemia-reperfusion injury,MIRI)的作用机制。方法通过中药系统药理学数据库及分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)检索四妙勇安汤活性成分和作用靶点,通过OMIM、GeneCards、PharmGkb三个数据库筛选巨噬细胞和MIRI的主要靶点,构建药物—成分—靶点网络,进行网络拓扑学分析后获得药物主要活性成分;利用STRING 12.0进行蛋白质互作分析,构建PPI网络以筛选关键靶点及核心靶点;运用David库对关键交集靶点进行GO和KEGG富集分析;利用Cytoscape 3.10.2将分析得到的关键通路、交集靶点和主要活性成分三者构建活性成分—靶点—通路网络并进行网络拓扑学分析,获取药物核心活性成分;进一步对核心活性成分和核心靶点的结合程度进行分子对接验证。结果筛选出四妙勇安汤重要活性成分有槲皮素、山奈酚、β-谷甾醇、木犀草素等,PPI网络中关键交集靶点29个,核心靶点有白介素(interleukin,IL)-6、IL-1β、肿瘤坏死因子(tumour necrosis factor,TNF)、信号传导及转录激活蛋白3(signal transducer and activator of transcription 3,STAT3)和丝氨酸/苏氨酸激酶1(serine/threonine kinase 1,Akt1)。富集分析得到细胞组成23条,分子功能54条,生物过程374条;KEGG通路富集分析得到147条,主要涉及晚期糖基化终产物—受体、癌症相关、脂质与动脉粥样硬化、IL-17等多条信号通路。分子对接结果可知,四妙勇安汤的核心活性成分槲皮素、山奈酚、β-谷甾醇、木犀草素、柚皮素等与核心靶点IL-6、TNF、IL-1β、STAT3、Akt1结合良好。结论通过网络药理学结合分子对接的方法预测了四妙勇安汤通过调控巨噬细胞改善MIRI的主要作用机制,可能是通过抑制炎症反应、氧化应激和心肌细胞凋亡发挥�Objective To explore the mechanism of Simiao Yong’an Decoction regulating macrophages to improve myocardial ischemia-reperfusion injury(MIRI)based on network pharmacology and molecular docking.Methods The active components and targets of Simiao Yong’an Decoction were searched by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP).The main targets of macrophage and MIRI were screened through OMIM,GeneCards and PharmGkb databases.The drug-component-target network was constructed,and the main active components of the drug were obtained after network topology analysis.STRING 12.0 was used for protein-protein interaction analysis,and PPI networks were constructed to screen key targets and core targets.The David library was used for GO and KEGG enrichment analysis of key intersecting targets.Cytoscape 3.10.2 was used to construct the active component-target-pathway network of the key pathways,intersection targets and main active components which were obtained through the analysis.Then performed network topology analysis to obtain the core active components of the drugs.The degree of binding between core active components and core targets are further demonstrated through molecular docking.Results The important active components of Simiao Yong’an Decoction were quercetin,kaempferol,beta-sitosterol,luteolin,etc.A total of 29 key intersection targets were obtained in the PPI network,the core targets include interleukin(IL)-6,IL-1β,tumour necrosis factor(TNF),signal transducer and activator of transcription 3(STAT3)and serine/threonine kinase 1(Akt1).Through enrichment analysis,23 cell compositions,54 molecular functions and 374 biological processes were obtained.A total of 147 pathways were obtained by KEGG pathway enrichment analysis.It mainly involves AGE-RAGE signaling pathway in diabetic complications,pathways in cancer,lipid and atherosclerosis,and IL-17 signaling pathway,etc.The results of molecular docking showed that the active components of Simiao Yong’an Decoction such

关 键 词：网络药理学 分子对接 四妙勇安汤 巨噬细胞 缺血再灌注损伤 

分 类 号：R259[医药卫生—中西医结合]