基于网络药理学和分子对接探究肾苏合剂治疗糖尿病肾病的机制

Exploring the mechanism of Shensu Mixture treating diabetic nephropathy based on network pharmacology and molecular docking

关键词:  肾苏合剂  糖尿病肾病  网络药理学  分子对接

Key words:  Shensu Mixture  diabetic nephropathy  network pharmacology  molecular docking

摘要:

[目的] 基于网络药理学和分子对接技术探究名老中医曹式丽教授“辛通畅络法”的代表方剂—肾苏合剂治疗糖尿病肾病（DN）的作用机制。[方法] 通过TCMSP、BATMAN平台筛选肾苏合剂的活性成分，通过R studio软件获取活性成分的相关靶点，并添加靶点名称的缩写，将方剂的靶点信息与Uniprot数据库信息进行规范化。通过 Gene Cards、OMIM、CTD数据库获取DN的相关靶点。运用韦恩图在线绘制平台获取药物、疾病的交集靶点，通过Cytoscape软件将“药物活性成分、疾病、靶点”可视化。将交集靶点输入STRING数据库进行分析，构建蛋白质-蛋白质相互作用（PPI）网络图，对交集靶点进行基因本体（GO）、京都基因与基因组百科全书（KEGG）富集分析。[结果] 共获得肾苏合剂活性成分66个，靶点504个，DN靶点2 646个，交集靶点243个。共获得PPI靶点241个（2个游离节点被删去），包括清蛋白基因（ALB）、AKT丝氨酸/苏氨酸激酶（AKT1）、白介素-6（IL-6）、肿瘤坏死因子（TNF）、胰岛素基因（INS）、白介素-1β（IL-1β）等。GO富集分析主要涉及：DNA-转录因子结合、RNA聚合酶Ⅱ-特异性DNA-转录因子结合、受体配体活性等。KEGG富集分析主要涉及：脂质和动脉粥样硬化、人巨细胞病毒感染、流体剪切应力与动脉粥样硬化等。[结论] 肾苏合剂可能通过多个靶点、通路治疗DN，本研究为肾苏合剂的临床使用提供了理论依据。

Abstract:

[Objective] Based on network pharmacology and molecular docking technology, this paper explored the mechanism of Shensu Mixture which is a representative prescription of “Xintong Changluo Method” put forward by Professor CAO Shili, treating diabetic nephropathy（DN）. [Methods] Active ingredients of Shensu Mixture were screened on TCMSP and BATMAN platform. The relevant targets of active ingredients were obtained by using R studio software and abbreviations of target names were added and normalized with the Uniprot database information. Targets of DN were obtained by Gene Cards, OMIM and CTD database. The intersection targets were obtained using the online mapping platform of Venn Diagram. Network diagram was visualized via Cytoscape software. The intersection targets were input into STRING database for analysis, protein-protein interaction（PPI） network diagram was constructed, Gene Ontology（GO） as well as Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analysis were performed. [Results] A total of 66 active ingredients, 504 targets of Shensu Mixture and 2646 DN targets were obtained. There were totally 243 intersection targets and 241 PPI targets（2 dissociate targets were deleted）, including ALB, AKT1, IL-6, TNF, INS, IL-1β, etc. GO enrichment analysis mainly involved DNA-binding transcription factor binding, RNA polymerase Ⅱ-specific DNA-binding transcription factor binding, receptor ligand activity, etc. KEGG enrichment analysis mainly involved Lipid and atherosclerosis, human cytomegalovirus infection, fluid shear stress and atherosclerosis, etc. [Conclusion] Shensu Mixture may treat DN through multiple targets and pathways, this paper provided theoretical basis for its clinical use.