基于网络药理学和分子对接探讨真武汤治疗扩张型心肌病的作用机制  

Mechanism of Zhenwu Decoction in the Treatment of Dilated Cardiomyopathy Based on Network Pharmacology and Molecular Docking

作　　者：孙斯嘉 冼绍祥[2] 杨忠奇[2] 尹克春[3] 袁天慧[2] SUN Sijia;XIAN Shaoxiang;YANG Zhongqi;YIN Kechun;YUAN Tianhui(Guangzhou University of Chinese Medicine,Guangzhou 510006,Guangdong,China)

机构地区：[1]广州中医药大学,广州510006 [2]广州中医药大学第一附属医院,广州510405 [3]广东省中医院,广州510120

出　　处：《中西医结合心脑血管病杂志》2022年第7期1173-1183,共11页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease

基　　金：国家自然科学基金项目(No.81704036);国家重点研发计划“中医药现代化”项目(No.2017YFC1700304);广东省自然科学基金项目(No.2017A030310128)。

摘　　要：目的基于网络药理学和分子对接的方法探讨真武汤治疗扩张型心肌病的作用机制。方法通过中药系统药理学数据库与分析平台(TCMSP)和Swiss Target Prediction网站获取真武汤有效化合物成分及相应的靶点,利用UniProt数据库将获得的靶点名称转换成基因名;通过在线人类孟德尔遗传数据库(OMIM)、基因名片数据库(GeneCard)、TTD数据库、毒性与基因比较数据库(CTD)、遗传药理学和药物基因组学数据库(PharmGKB)获取扩张型心肌病相关基因,将真武汤靶点基因和扩张型心肌病相关基因取交集作为真武汤治疗扩张型心肌病的潜在靶点;将交集基因导入STRING数据库进行蛋白互作分析,利用Cytoscape软件绘制真武汤中药-潜在化合物-潜在靶点的可视化网络关系图;应用RStudio的ClusterProfiler包对潜在靶点进行基因本体(GO)功能注释和京都基因和基因组百科全书(KEGG)通路富集分析,使用Pathview包进行代谢途径整合和可视化;最后将筛选的关键靶蛋白进行分子对接验证。结果通过筛选得到真武汤有效化合物成分59个,对应药物靶点259个,扩张型心肌病相关靶点980个,潜在靶点47个,筛选出41个与疾病相关的有效化合物,GO功能注释分析到943条,KEGG富集分析到120条信号通路。其中β-谷甾醇、山奈酚、3β-乙酰氧基苍术酮、去甲乌头碱、芍药新苷、多根乌头碱、茯苓酸B、常春藤皂苷元等为真武汤治疗扩张型心肌病的主要活性化合物,白细胞介素6(IL6)、肿瘤坏死因子(TNF)、转录激活因子3(STAT3)、表皮生长因子受体(EGFR)、内皮一氧化氮合酶(NOS3)等为关键靶点,主要通过调控晚期糖基化终末产物-糖基化终末产物受体(AGE-RAGE)、缺氧诱导因子-1(HIF-1)、弓形虫、脂肪细胞脂解、肾素分泌、钙离子等信号通路发挥治疗作用。结论真武汤可能通过β-谷甾醇、山奈酚、3β-乙酰氧基苍术酮、去甲乌头碱、芍药新苷等�Objective To explore the mechanism of Zhenwu Decoction in the treatment of dilated cardiomyopathy based on network pharmacology and molecular docking.Methods The active compounds and corresponding targets of Zhenwu Decoction were obtained through traditional Chinese medicine(TCM)system pharmacology database and analysis platform(TCMSP)and Swiss target Prediction website,and the target names were converted into gene names by Uniprot database.Genes related to dilated cardiomyopathy were obtained from online Mendelian inheritance in man(OMIM),GeneCard database(GeneCard),therapeutic target database(TTD),comparative toxicogenomics database(CTD),and pharmacogenomics and pharmacogenomics database(PharmGKB).The intersection of Zhenwu Decoction target genes and dilated cardiomyopathy related genes were selected as the potential targets of Zhenwu Decoction in the treatment of dilated cardiomyopathy.The intersection genes were imported into STRING database for protein interaction analysis,and the visual network diagram of Zhenwu Decoction-potential compound-potential target was drawn by Cytoscape software.RStudio′s ClusterProfiler package was used for gene ontology(GO)functional annotation and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis for potential targets,and the Pathview package was applied to represent metabolic pathway integration and visualization.Finally,the key target proteins were screened for molecular docking verification.Results 59 active compounds,259 corresponding drug targets,980 dilated cardiomyopathy related targets,47 potential targets,41 disease-related active compounds were screened out.The number of GO functional annotation analysis was 988,and KEGG enrichment analysis was 120.Among them,beta-sitosterol,kaempferol,3β-acetoxylatractyloxone,(R)-norcoclaurine,lactiflorin,karakoline,poricoic acid B,hederagenin,etc were the main active compounds in Zhenwu Decoction for the treatment of dilated cardiomyopathy.Interleukin6(IL6),tumor necrosis factor(TNF),transcription activator

关 键 词：扩张型心肌病 真武汤 网络药理学 分子对接 作用机制 

分 类 号：R73[医药卫生—肿瘤]