基于网络药理学和分子对接探讨丹参抗放射性心肌纤维化的机制

Mechanism of Salvia Miltiorrhiza Against Radioactive-induced Myocardial Fibrosis Based on Network Pharmacology and Molecular Docking

目的:采用网络药理学和分子对接探讨丹参抗放射性心肌纤维化的分子机制。方法:在中药系统药理学数据库与分析平台(TCMSP)进行药物成分和相应靶点筛选,疾病靶点通过基因名片数据库(GeneCards)、在线人类孟德尔遗传数据库(OMIM)和治疗靶点数据库(TTD)获得,在Venny 2.1.0平台上提取二者共同靶点。运用STRING数据库与Cytoscype 3.9.1软件建立蛋白互作(PPI)网络,对PPI网络行拓扑学分析得到的核心靶点导入Metascape数据库进行功能富集分析,经Cytoscype 3.9.1软件构建“活性成分-核心靶点-信号通路”网络。最后,利用AutoDockTools 1.5.6软件进行分子对接验证,可视化由PyMOL 2.2.0软件完成。结果:共获取药物活性成分59种,相应靶点137个,疾病靶点3042个,交集靶点100个。PPI网络拓扑学分析所得的蛋白激酶B1(AKT1)、肿瘤坏死因子(TNF)、肿瘤蛋白p53(TP53)等22个核心靶点,主要通过TNF信号通路、缺氧诱导因子1(HIF-1)信号通路、丝裂原激活蛋白激酶(MAPK)信号通路等途径发挥功能,与丹参中毛地黄黄酮、丹参酮ⅡA、2-异丙基-8-甲基菲-3,4-二酮等活性成分有关。分子对接结果显示,核心靶点与核心成分间结合紧密,结构稳定。结论:丹参治疗放射性心肌纤维化具有多成分、多靶点、多通路的特点,可为今后临床应用提供理论基础。

Objective:To investigate the molecular mechanism of Salvia miltiorrhiza against radioactivity-induced myocardial fibrosis using network pharmacology and molecular docking.Methods:Drug components and corresponding targets were screened on Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP).The disease targets were obtained from GeneCards,Online Mendelian Inheritance in Man(OMIM),and Therapeutic Target Database(TTD);the common targets were extracted by the Venny 2.1.0 platform.The STRING database and Cytoscype 3.9.1 software were used to establish the protein-protein interaction(PPI)network;the core targets obtained from the topological analysis of the PPI network were imported into the Metascape database for functional enrichment.Cytoscype 3.9.1 software was used to construct the"active ingredient-core target-signaling pathway"network.Finally,the molecular docking verification was performed using AutoDockTools 1.5.6 software,and the result visualization was completed by PyMOL 2.2.0 software.Results:A total of 59 drug active ingredients were obtained,including 137 corresponding targets,3042 disease targets,and 100 intersection targets were obtained.The 22 core targets(protein kinase B1(AKT1),tumor necrosis factor(TNF),tumor protein p53(TP53),etc.obtained from the analysis of PPI network topology played the role through the TNF signaling pathway and hypoxia-inducible factor-1(HIF-1)signaling pathway,mitogen-activated protein kinase(MAPK)signaling pathway,and other pathways.They were related to active ingredients such as luteolin,tanshinoneⅡA,and 2-isopropyl-8-methylphenanthrene-3,4-dione in Salvia miltiorrhiza.The molecular docking results showed that the core target and components were closely combined,and the structure was stable.Conclusion:Salvia miltiorrhiza treats of radiation-induced myocardial fibrosis by component,multi-target,and multi-channel,which can provide a theoretical basis for future clinical application.