基于网络药理学研究益肾清利颗粒对IgA肾病的作用机制

Study on the mechanism of Yishen-Qingli granule in treating IgA nephropathy based on network pharmacology

目的通过网络药理学探讨益肾清利颗粒对IgA肾病的作用机制。方法通过TCMSP筛选益肾清利颗粒8味中药的相关成分及作用靶点,于Uniprot数据库将作用靶点转换成基因,使用Cytoscape 3.6.0构建药物活性成分-靶点网络;通过人类基因组数据库(GeneCards)筛选IgA肾病相关靶标,将药物及疾病靶点导入Venny 2.1软件取交集,得到的共有靶标上传于STRING平台构建蛋白质互作网络,借助生物信息资源数据库对生成结果进行GO及KEGG富集分析,并构建"益肾清利颗粒成分-靶点-信号通路"多维网络。结果筛选得到69个活性成分,包括人参皂苷、β-谷甾醇、谷甾醇、槲皮苷等。得到益肾清利颗粒作用于IgA肾病的靶点94个,其中核心靶点30个,主要包括Jun原癌基因(JUN)、TNF、肿瘤蛋白p53(TP53)、AKT1及IL-6等。KEGG富集分析结果主要涉及3条通路,分别是PI3K-AKT通路、TNF炎症通路及MAPK通路。结论益肾清利颗粒通过多成分、多靶点、多途径作用于IgA肾病,本研究通过网络药理学探讨益肾清利颗粒的治疗机制,为进一步实验研究奠定基础。

Objective To explore the molecular mechanism of Yishen-Qingli granules in treating IgA nephropathy through network pharmacology.Methods The relevant components and functional targets of 8 Chinese herbs of Yishen-Qingli granules were screened through the TCMSP.The functional targets were converted into genes in the Uniprot database.Cytoscape 3.6.0 was used to construct the active ingredients-target network;screening IgA nephropathy-related targets through the Human Genome Database(GeneCards),importing drug and disease targets data into Venny2.1 software for intersection,and uploading the shared targets to the STRING platform to build a protein interaction network.With the help of bioinformatics resource database,GO and KEGG enrichment analysis were carried out on the generated results,and the multi-dimensional network of"Yishen-Qingli granule composition target signal pathway"was constructed.Results 69 active ingredients were screened,including ginsenoside,beta-sitosterol,sitosterol,and quercetin.There were 94 Yishen-Qingli granules for IgA nephropathy,including 30 core targets,including JUN,TNF,TP53,AKT1,and IL-6.KEGG enrichment analysis mainly involve three pathways,namely PI3K-Akt pathway,TNF inflammation pathway and MAPK pathway.Conclusions Yishen-Qingli granules can treat IgA nephropathy in multi-component,multi-target and multi-pathway way.This study initially explored the therapeutic mechanism of Yishen-Qingli granules through network pharmacological analysis,and laid the foundation for further experimental research.