基于网络药理学探讨水蛭治疗急性心肌梗死的作用机制  

The Mechanism of Leech in the Treatment of Acute Myocardial Infarction Based on Network Pharmacology

作　　者：欧阳嘉慧 孟闫燕[1] 张帆[1] 林宫羽 杜天依 李立志[2] 高铸烨[2] OUYANG Jiahui;MENG Yanyan;ZHANG Fan;LIN Gongyu;DU Tianyi;LI Lizhi;GAO Zhuye(Beijing University of Chinese Medicine,Beijing 100029,China)

机构地区：[1]北京中医药大学,北京100029 [2]中国中医科学院西苑医院,国家中医心血管病临床医学研究中心,北京100091

出　　处：《中西医结合心脑血管病杂志》2022年第24期4417-4424,共8页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease

基　　金：国家十二五科技支撑计划(No.2013BAI02B01);国家“重大新药创制”科技重大专项(No.2019ZX09201005-002-006);北京市中医药科技发展资金项目(No.JJ-2020-79);中国中医科学院科技创新工程重大攻关项目(No.I2021A00920)。

摘　　要：目的 基于网络药理学方法探讨水蛭治疗急性心肌梗死(AMI)的作用机制。方法 通过BATMAN-TCM数据库收集水蛭的活性成分及对应靶点;通过GeneCards、OMIM、TTD、DrugBank数据库收集AMI疾病靶点,使用Venny 2.1.0在线工具对疾病及药物靶基因进行映射绘制韦恩图,获得水蛭治疗AMI的潜在作用靶点,利用Cytoscape 3.7.2软件构建“药物-活性成分-靶点-疾病”网络图。通过STRING数据库获取作用靶点之间的互作关系,并导入Cytoscape 3.7.2软件构建蛋白-蛋白互作(PPI)网络。通过Metascape数据库对水蛭治疗AMI的作用靶点进行基因本体(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路富集分析。结果 共获得水蛭13个活性成分,包括藏红花酸、熊果酸、L-半乳庚酮糖、D-甘露庚酮糖等;342个作用靶点,其中64个作用靶点与AMI相关。PPI网络分析提示胰岛素(INS)、清蛋白(ALB)、肿瘤坏死因子(TNF)、白细胞介素1β(IL1β)等可能为水蛭治疗AMI的核心靶点;KEGG信号通路富集分析主要包括非酒精性脂肪肝、癌症通路、癌症中的蛋白聚糖、神经活性配体-受体相互作用信号通路、钙信号通路等20条通路。结论 水蛭可能通过多成分、多靶点、多通路发挥治疗AMI的作用,为水蛭治疗AMI的临床应用及制剂研发提供理论依据。Objective To explore the mechanism of leech in the treatment of acute myocardial infarction(AMI) based on network pharmacology.Methods The active ingredients and corresponding targets of leech were collected through BATMAN-TCM database.The disease targets of AMI were screened out by GeneCards, OMIM,TTD and DrugBank databases.The Venn 2.1.0 online tool was used to draw a Venny map and to obtain the potential targets of leech in treating AMI,and then the "drug-active components-target-disease" network map was constructed by Cytoscape 3.7.2 software.The interrelationship between the potential targets was obtained through STRING database and imported into Cytoscape 3.7.2 software to construct protein-protein interaction(PPI) network.Gene Ontology(GO) analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis for the targets were conducted using Metascape database.Results A total of 13 active components of leech were obtained, including crocetin, ursolic acid, L-galactoheptulose, D-mannoheptulose.A total of 342 action targets were obtained, of which 64 targets were related to AMI.PPI network analysis showed that insulin(INS),albumin(ALB),tumor necrosis factor(TNF),interleukin1β(IL1β) were the core target of leech to treat AMI.KEGG pathway enrichment analysis mainly related 20 pathways including non-alcoholic fatty liver disease, pathways in cancer, proteoglycans in cancer, neuroactive ligand-receptor interaction, calcium signaling pathway and other pathways.Conclusion Leech might play a role in the treatment of AMI through multi-component, multi-target and multi-pathway, providing a theoretical basis for the clinical application and preparation development of leech in the treatment of AMI.

关 键 词：急性心肌梗死 水蛭 网络药理学 机制 

分 类 号：R285[医药卫生—中药学]