基于网络药理学研究“黄芪-大黄-积雪草”角药治疗慢性肾功能衰竭的作用机制

Mechanism of action of“Huangqi-Dahuang-Jixuecao”triangle drug combination in the treatment of chronic renal failure based on network pharmacology

目的通过网络药理学方法研究“黄芪-大黄-积雪草”治疗慢性肾功能衰竭(chronic renal failure,CRF)的核心成分、作用靶点、信息通路及作用机制。方法通过中药系统药理学数据库与分析平台(TCMSP)获取并筛选“黄芪-大黄-积雪草”角药的活性成分及作用靶点,CRF相关靶基因通过GeneCards、人类孟德尔遗传数据库和疾病关联数据库(GAD)数据库检索,对CRF的相关靶点及“黄芪-大黄-积雪草”角药的作用靶点取交集,其中蛋白信息转换成基因信息通过Uniprot数据库完成,绘制Venny图。将靶点导入STRING数据库制作蛋白质相互作用(PPI)网络图,通过Cytoscap3.9.1软件对PPI网络进一步分析,得到关键蛋白靶点。借助京都基因与基因组百科全书(KEGG)与注释、可视化和集成发现数据库(DAVID)数据库进行基因本体(GO)功能及KEGG信号通路富集分析。应用Cytoscape 3.9.1软件构建“黄芪-大黄-积雪草”角药治疗CRF的疾病-通路-靶点-成分-药物网络图。结果获得“黄芪-大黄-积雪草”共39种活性成分、226个靶点,其中黄芪-大黄-积雪草角药治疗CRF关键靶点82个。PPI网络图显示78个节点,互作关系269条,平均度值为6.9。GO分析共得到富集结果614个,KEGG分析得到142条信号通路,涉及晚期糖基化终未产物(AGE-RAGE)信号通路、癌症通路、肿瘤坏死因子(TNF)信号通路、白细胞介素(IL)-17信号通路、Toll样受体信号通路等。结论“黄芪-大黄-积雪草”角药可通过多种成分、多个靶点、多条信号通路治疗CRF。

Objective To investigate the core components,targets,signaling pathways,and mechanisms of action of"Huangqi-Dahuang-Jixuecao"in the treatment of chronic renal failure(CRF)through network pharmacology.Methods The active ingredients and targets of the"Huangqi-Dahuang-Jixuecao"triangle drug combination were obtained and screened through the TCMSP database and analysis platform.The CRF-related target genes were searched through GeneCards,Human Mendelian Genetic Database,and GAD Database.Subsequently,the intersection of the CRF-related targets and the action targets of the"Huangqi-Dahuang-Jixuecao"triangle drug combination was taken.The protein information was converted into gene information using the UniProt database,and a Venn diagram was constructed.Import the target into the STRING database to create a protein interaction network diagram,and further analyze and map the PPI network using Cytoscape 3.9.1 software to obtain key protein targets.Perform GO function and KEGG signaling pathway enrichment analysis using KEGG and DAVID databases.Using Cytoscape 3.9.1 software to construct a disease pathway target component drug network diagram for the treatment of CRF with"Huangqi-Dahuang-Jixuecao"triangle drug combination.Results A total of 39 active ingredients and 226 targets were obtained from"Huangqi-Dahuang-Jixuecao",among which 82 key targets were identified for the treatment of CRF with"Huangqi-Dahuang-Jixuecao"triangle drug combination.The protein-protein interaction network diagram showed 78 nodes and 269 interaction relationships,with an average degree of 6.9.GO analysis yielded a total of 614 enrichment results,while KEGG analysis identified 142 signaling pathways,including AGE-RAGE signaling pathway,cancer pathway,TNF signaling pathway,IL-17 signaling pathway,Toll like receptor signaling pathway,and more.Conclusion"Huangqi-Dahuang-Jixuecao"triangle drug combination can treat CRF through multiple components,targets,and signaling pathways,providing a basis for further research and having certain reference value.