水飞蓟素治疗药物性肝损伤的“药效—靶标”作用网络分析

Study on Mechanisms of Silymarin in the Treatment of Drug-induced Liver Injury Based on Network Pharmacology

目的:通过网络系统药理学筛选并探讨水飞蓟素治疗药物性肝损伤的药效靶点,以期为临床的精准治疗提供参考。方法:通过TCMSP与CTD数据库获取水飞蓟素靶点对应的基因;从GEO、GeneCards以及OMIM数据库获得药物性肝损伤的疾病基因,与水飞蓟素的靶点基因取交集,筛出药效靶点,运用Cytoscape软件和String数据库制成“成分—靶点”网络及PPI网络图。运用R语言中的clusterProfiler包对药效靶点进行GO及KEGG富集分析;运行Autodock vina软件对药效靶点进行分子对接。结果:筛选得到交集基因112个,STAT3、TNF、RELA等为主要作用靶点。GO/KEGG富集分析共获得涉及免疫炎症反应、肝脏代谢、氧化应激等的生物过程和相关通路。分子对接显示药效靶点与水飞蓟素能良好结合。结论:水飞蓟素可能通过STAT3、TNF、RELA等多个炎症靶标调控参与多条肝脏代谢通路,从而发挥其抗药物性肝损伤的作用。

Objective:To explore the potential mechanism of Silymarin in the treatment of drug-induced liver injury(DILI)based on network pharmacology and molecular docking.Methods:The active components and corresponding targets of Silymarin were obtained by TCMSP and CTD databases.The disease genes of drug-induced liver injury were obtained from GEO,GeneCards and OMIM databases,and intersection genes of target genes of Silymarin were screened.The drug active ingredients-target network diagram was drawn by Cytoscape software.PPI protein interactions Network was constructed by String database.R software and clusterProfiler package were used to carry out GO and KEGG enrichment analysis on the intersection target.Autodock vina software was used to carry out molecular docking between Silymarin and therapeutic targets.Results:Totally 112 intersection genes were screened out.STAT3,TNF,RELA are the main therapeutic targets.After GO function enrichment analysis and KEGG enrichment analysis,obtaining biological processes and related pathways involving immune inflammatory response,liver metabolism and oxidative stress.Molecular docking showed that the target protein could bind the Silymarin.Conclusion:Silymarin can control STAT3,TNF,RELA and other core genes to regulate many signaling pathways of inflammatory response,liver metabolism and oxidative stress.