基于网络药理学和分子对接技术分析疏血通注射液治疗缺血性脑卒中的作用机制

Analysis of the mechanism of Shuxuetong injection on treating cerebral ischemic stroke based on network pharmacology and macromolecular docking technology

目的构建疏血通注射液活性成分—作用靶点和蛋白质相互作用网络,分析疏血通注射液治疗缺血性脑卒中(CIS)的作用机制。方法通过BATMAN-TCM数据库收集疏血通注射液中水蛭和地龙的成分并查阅文献进行补充,通过SwissADME平台筛选获得疏血通注射液活性化合物;通过SwissTargetPrediction预测活性成分的潜在靶点,并与GeneCards数据库中CIS的疾病靶点数据取交集获得共同靶点,进行蛋白质—蛋白质相互作用(PPI)分析,使用Cytoscape构建“药物—靶点—疾病”网络并进行分析;通过DAVID数据库对共同靶点进行GO富集和KEGG通路富集分析。采用AutoDock Tools 1.5.7、AutoDock Vina 1.2.0将得到的关键活性成分和核心靶点进行分子对接。结果筛选得到疏血通注射液活性成分88个和治疗CIS潜在靶点351个及主要活性成分10个;疏血通注射液治疗CIS的关键靶点为SRC、ESR1、SIRT1、CTNNB1、STAT3等;可能参与的通路有癌症途径、神经元神经活性配体—受体相互作用、脂质与动脉粥样硬化、钙离子信号、CAMP信号等通路。结论疏血通注射液的主要活性成分为(S)-2-{[(苄氧基)羰基]氨基}-5-乙氧基-5-氧代戊酸、水蛭素A等,可能通过作用于SRC、ESR1等关键靶点,在癌症途径等通路发挥治疗CIS的作用。

Objective To construct a network of active ingredients,targets,and protein interactions for Shuxuetong injection,and analyze the mechanism of action of Shuxuetong injection in the treatment of cerebral ischemic stroke(CIS).Methods Collected the components of leeches and earthworms in Shuxuetong injection through the BATMAN-TCM database and supplemented them with literatures review.Screened the active compounds of Shuxuetong injection through the SwissADME platform.Predicted potential targets of active ingredients through SwissTargetPrediction,and obtained common targets by intersecting with CIS disease target data in the GeneCards database,then conducted PPI analysis,and used Cytoscape to construct a"drug target disease"network for analysis.GO enrichment and KEGG pathway enrichment analysis were conducted on common targets through the DAVID database.Used AutoDock Tools 1.5.7 and AutoDock Vina 1.2.0 to perform macromolecular docking between the obtained key active ingredients and core targets.Results The toal of 88 active ingredients of Shuxuetong injection,351 potential targets on treating CIS,and 10 main active ingredients were screened out.The key targets of Shuxuetong injection for CIS were SRC,ESR1,SIRT1,CTNNB1,STAT3,etc.The possible pathways involved included cancer pathway,neural active ligand receptor interaction,lipid and atherosclerosis,calcium signal,CAMP signal,etc.Conclusion The main active ingredients of Shuxuetong injection are(S)-2-{[(benzyloxy)carbonyl]amino}-5-ethoxy-5-oxyvaleric acid,hirudin A,etc,which may play a role in the treatment of CIS in cancer pathways and other pathways by acting on key targets such as SRC and ESR1.