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基于网络药理学及分子对接技术探究润肺益肾饮治疗糖尿病肾病的作用机制
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Abstract:
目的：利用网络药理学方法来探讨润肺益肾饮治疗糖尿病肾病的作用机制。方法：通过TCMSP数据库获取润肺益肾饮的主要化学成分及其靶点，并运用UniProt数据库和SwissTargetPrediction数据库对靶点信息进行矫正和补充；通过Genecards数据库，筛选糖尿病肾病的相关靶点；利用bioinformatics网站，获取药物和疾病的交集靶点；通过Cytoscape 3.9.1软件构建“药物–成分–靶点”网络；采用STRING数据库构建PPI网络，获取关键靶点；对交集靶点进行基因本体论(GO)和京都基因和基因组百科全书(KEGG)通路富集分析；此外，通过分子对接实验对核心成分和关键靶点进行对接验证。结果：通过筛选得到润肺益肾饮活性成分56个以及相应的作用靶点630个，得到糖尿病肾病相关的基因靶点1022个，二者共同靶点172个。进一步网络分析显示，主要活性成分为β-谷甾醇、槲皮素、花生四烯酸、啤酒甾醇等；关键靶点为SRC、STAT3、MAPK3、MAPK1、AKT1、EGFR等；KEGG富集分析交集靶点主要富集在AGE-RAGE信号通路中；分子对接结果显示核心成分与核心靶点具有较好的构象。结论：润肺益肾饮对于糖尿病肾病的治疗具有多成分、多靶点、多通路的特点，可能通过抑制炎症、抗纤维化、调控自噬等发挥治疗糖尿病肾病的作用。
Objective: this paper uses network pharmacology to explore the mechanism of Runfei Yishen Decoction in the treatment of diabetes nephropathy by network pharmacology. Methods: The main chemical components and targets of Runfei Yishen Decoction were obtained through TCMSP database, and the target information was corrected and supplemented by UniProt database and SwissTargetPrediction database. Through the Genecards database, relevant targets of diabetic nephropathy were screened; use the Bioinformatics website to access targets at the intersection of drugs and diseases; build a drug-ingredient-target network through Cytoscape 3.9.1 software; the STRING database is used to construct a PPI network to obtain key targets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of intersection targets; in addition, the core components and key targets were verified by molecular docking experiments. Results: Through screening, 56 active ingredients and 630 corresponding targets were obtained, and 1022 gene targets related to diabetic nephropathy were obtained, and 172 common targets were obtained. Further network analysis showed that the main active ingredients were beta-sitosterol, quercetin, arachidonic acid (AA), cerevisterol, etc. The key targets are SRC, STAT3, MAPK3, MAPK1, AKT1, EGFR, etc. The key targets of KEGG enrichment analysis were mainly enriched in the AGE-RAGE signaling pathway. The results of molecular docking showed that the core components and the core targets had good conformation. Conclusion: Runfei Yishen Decoction has the characteristics of multi-component, multi-target and multi-pathway for the treatment of diabetic nephropathy, and may play a role in the treatment of diabetic nephropathy by inhibiting inflammation, anti-fibrosis and regulating autophagy.
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