基于网络药理学联合分子对接技术探讨肾疏宁防治肾间质纤维化的作用机制

Mechanism of Shenshuning in preventing and treating renal interstitial fibrosis based on network pharmacology and molecular docking technique

关键词:  肾疏宁  肾间质纤维化  网络药理学  分子对接  信号通路

Key words:  Shenshuning  renal interstitial fibrosis  network pharmacology  molecular docking  signaling pathway

摘要:

[目的] 基于网络药理学探讨肾疏宁防治肾间质纤维化的潜在机制。[方法] 通过检索TCMSP、Uniprot等数据库获得肾疏宁中药的化学成分，并找出其对应的靶点。通过GeneCards、OMIM、TTD 等数据库筛选药物靶点和疾病靶点。运用Cytoscape软件构建“成分-靶标-通路-疾病”网络；进而对靶点进行KEGG信号通路富集和GO功能富集分析。借助AutoDock软件，将受体与配体进行预处理及分子对接。[结果] 共筛选出肾疏宁作用于肾间质纤维化的主要活性成分130种，相关作用靶点116个。KEGG分析结果显示这些靶点主要富集映射在肿瘤坏死因子(TNF)、核因子激活的B细胞的κ-轻链增强(NF-κB)、晚期糖基化终产物及其受体(AGE-RAGE)等高度相关的信号通路。GO富集结果表明肾疏宁治疗肾间质纤维化可能通过炎症反应、细胞凋亡、氧化应激反应等过程发挥作用。分子对接结果显示肾疏宁有效活性成分豆甾醇、丹参酮、异鼠李素与核心靶点之间具有较好的结合活性；核心靶点TNF、RELA与有效成分的结合活性较好。[结论] 肾疏宁可能通过多种途径防治肾间质纤维化。

Abstract:

[Objective] To explore the potential mechanism of Shenshuning in preventing and treating renal interstitial fibrosis based on network pharmacology.[Methods] The chemical constituents of Shenshuning were obtained by searching TCMSP,Uniprot databases,and the corresponding target were found. Drug targets and disease targets were screened by Genecards,OMIM,TTD databases. The "component-target-pathway-disease" network was constructed by Cytoscape software. Then,KEGG signaling pathway enrichment and GO function enrichment were analyzed on the target. With the help of AutoDock software,the receptor and ligand were preprocessed and molecular docking.[Results] A total of 130 active components and 116 related targets of Shenshuning on renal interstitial fibrosis were screened out. KEGG analysis showed that these targets were mainly enriched in TNF,NF-κB,AGE-RAGE and other highly correlated signaling pathways. GO enrichment results showed that Shenshuning may play a role in the treatment of renal interstitial fibrosis through the regulation of inflammatory response,cell apoptosis,oxidative stress reaction and other processes. The molecular docking results showed that the active components of Shenshuning showed good binding activity among stigmasterol,tanshinone and isorhamnetin and the core targets. The binding activity of TNF and RELA with active components were better.[Conclusion] Shenshuning may prevent and treat renal interstitial fibrosis through various ways.