壮肾固精方治疗IgA肾病的网络药理学机制

Network Pharmacological Mechanisms of Zhuangshen Gujing Prescription in the Treatment of IgA Nephropathy

【目的】基于网络药理学预测壮肾固精方治疗IgA肾病的作用机制,为后续相关实验研究提供理论基础。【方法】通过TCMSP数据库和TCMID数据库获得壮肾固精方的有效化学成分和作用靶点,通过OMIM数据库、GeneCards数据库及PharmGkb数据库获得IgA肾病的相关基因,取交集后得到壮肾固精方和IgA肾病的核心基因。使用STRING数据库构建靶标蛋白质间互作(PPI)网络,使用Cytoscape软件构建药物有效成分-靶基因网络并进行拓扑分析。最后,应用R语言将共有靶点进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)富集分析。【结果】共获得壮肾固精方的有效成分57种、1 213个IgA肾病相关基因。有效成分-靶基因网络拓扑分析得到度值前5位的有效成分为槲皮素、木犀草素、山柰酚、黄芩素、刺芒柄花素,度值前5位的靶点为PTGS2、PTGS1、PRSS1、DPP4、ESR1。GO分析显示生物学进程主要与氧化应激相关;KEGG富集分析结果显示壮肾固精方治疗IgA肾病可能与核因子KappaB(NF-κB)信号通路、白细胞介素7(IL-7)信号通路、肿瘤坏死因子(TNF)信号通路有关。【结论】壮肾固精方可能主要通过调控细胞炎症反应和氧化应激过程发挥治疗IgA肾病的作用。

Objective To predict the mechanisms of Zhuangshen Gujing Prescription in the treatment of IgA nephropathy based on network pharmacology,and to provide theoretical basis for subsequent experimental studies.Methods The effective chemical constituents and effect targets of Zhuangshen Gujing Prescription were retrieved from TCMSP database and TCMID database, the related genes of IgA nephropathy were retrieved from OMIM database,GeneCards database and PharmGkb database,and the core genes of Zhuangshen Gujing Prescription and IgA nephropathy were obtained by intersection. The target protein-protein interaction(PPI)network was constructed using STRING database, and the active components-target genes network was constructed using Cytoscape for topological analysis. Finally,R language was used for gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)enrichment analysis with common targets. Results A total of 57 kinds of active components of Zhuangshen Gujing Prescription were obtained, and 1 213 IgA nephropathy related genes were acquired. According to the network topology analysis of the active components-target genes,the top 5 effective genes for degree were quercetin,luteolin,kaempferol,baicalein and formononetin. The top 5 effective targets for degree were PTGS2, PTGS1, PRSS1, DPP4 and ESR1. GO enrichment analysis showed that the biological process was mainly related to oxidative stress. The results of KEGG enrichment analysis showed that the treatment of IgA nephropathy with Zhuangshen Gujing Prescription may be related to nuclear factor KappaB(NF-κB)signaling pathway, interleukin 7(IL-7)signaling pathway and tumor necrosis factor(TNF)signaling pathway.Conclusion Zhuangshen Gujing Prescription plays a role in the treatment of IgA nephropathy possible by mainly regulating cellular inflammatory response and oxidative stress.