基于网络药理学探讨独活寄生汤治疗类风湿关节炎作用机制

目的运用网络药理学方法探讨独活寄生汤治疗类风湿关节炎的作用机制,使中药在防治类风湿关节炎中发挥更大的临床作用。方法通过检索中药系统药理学数据库(TCMSP)获得独活寄生汤方药中各味药物的有效活性成分及相关靶点,类风湿关节炎的疾病数据通过OMIM和Genecards数据库获取,运用R×643.6.1软件绘制药物-疾病韦恩图并获取交集靶点,运用Cytoscape3.7.1软件构建药物-成分-靶点-疾病相互作用网络,String数据库生成独活寄生汤治疗类风湿关节炎的蛋白与蛋白相互作用(PPI)网络,R×643.6.1软件分别对PPI网络中关键蛋白进行可视化、交集靶点基因本体(GO)分类富集分析,京都基因与基因组百科全书(KEGG)通路分析。结果在TCMSP数据库得到独活寄生汤有效成分1973个及靶点18562个,药物与疾病交集靶点有51个,PPI网络中关键蛋白有29个,GO富集分析得到20个条目,KEGG通路富集分析得到17条,并推断其作用机制可能与IL-6、CXCL8、VEGFA、IL1B、PTGS2、CCL2、MMP9、IL10、STAT3、JUN基因有关,并且IL-17信号通路、糖尿病并发症中的AGE-RAGE信号通路、TNF信号通路、Toll样受体信号通路、NOD样受体信号通路可能起着关键性的作用。结论基于网络药理学的方法验证了独活寄生汤治疗类风湿关节炎多成分-多靶点-多通路的作用特点,为进一步开展独活寄生汤治疗类风湿关节炎作用机制研究提供了新的思路和方法。

Study on the Mechanism of Duhuo Jisheng Decoction in the Treatment of Rheumatoid Arthritis Based on Network Pharmacology

Objective To explore the mechanism of Duhuo Jisheng Decoction(独活寄生汤)in treating rheumatoid arthritis by using network pharmacology,and to play a greater clinical role for traditional Chinese medicine in preventing and treating rheumatoid arthritis.Methods Retrieve the effective active ingredients and related targets of each drug in Duhuo Jisheng Decoction by searching the TCMSP database.The rheumatoid arthritis disease data is obtained through the OMIM and Genecards databases.R×643.6.1 software was used to draw the drug-disease venn diagram and obtain the intersection targets,Cytoscape 3.7.1 software was used to build a drug-ingredient-target-disease interaction network,the String database generates a protein-protein interaction(PPI)network for Duhuo Jisheng Decoction to treat rheumatoid arthritis,R×643.6.1 software was used to visualize key proteins in PPI networks,classify enrichment analysis of target gene ontology(GO)and pathway analysis of Kyoto Gene and Genome Encyclopedia(KEGG).Results In the TCMSP database,we obtained 1973 active ingredients of Duhuo Jisheng Decoction and 18562 targets,51 targets for drug and disease intersection,29 key proteins in PPI network,20 items in GO enrichment analysis,and KEGG pathway rich 17 results were collected from the analysis,and it was inferred that the mechanism of action may be related to IL-6,CXCL8,VEGFA,IL1 B,PTGS2,CCL2,MMP9,IL10,STAT3,JUN genes,and IL-17 signaling pathway,AGE in diabetes complications-RAGE signaling pathway,TNF signaling pathway,Toll-like receptor signaling pathway,NOD-like receptor signaling pathway may play a key role.Conclusion Based on network pharmacology,we verificated the multi-component-multi-target-multi-pathway characteristics of Duhuo Jisheng Decoction in treating rheumatoid arthritis,and provided new ideas and methods for further research on the mechanism of Duhuo Jisheng Decoction in treating rheumatoid arthritis.