基于网络药理学探讨独活寄生汤治疗类风湿关节炎与骨关节炎的“异病同治”机制

Network pharmacological analysis of Duhuo Jisheng Decoction for treating different diseases with same method on rheumatoid arthritis and osteoarthritis

关键词:  网络药理学  独活寄生汤  类风湿关节炎  骨关节炎  异病同治  机制

Key words:  network pharmacology  Duhuo Jisheng Decoction  rheumatoid arthritis  osteoarthritis  treating different diseases with same method  mechanism

摘要:

[目的] 基于网络药理学的方法，从靶点及生物学通路的角度探讨独活寄生汤治疗类风湿关节炎（RA）和骨关节炎（OA）的“异病同治”机制。[方法] 利用中药系统药理学数据库和分析平台、中药分子机制生物信息学分析工具、环球蛋白资源数据库及人类疾病基因数据库等资源预测独活寄生汤治疗RA和OA的靶点。利用在线工具Venny得到共有靶点后再运用蛋白相互作用网络分析数据库构建共有靶点之间的蛋白相互作用网络，运用Cytoscape软件绘制独活寄生汤对于RA和OA“异病同治”的作用机制网络，并分别利用网络分析插件和分子复杂检测插件进行拓扑分析和聚类分析。运用注释、可视化和综合发现数据库进行生物学过程和通路富集分析。[结果] 独活寄生汤治疗RA和OA共有194个共有靶点，特有靶点分别为80个和28个。对共有靶点的模块化分析得到5个模块，主要模块参与10个主要相关信号通路，可体现于滑膜细胞增生侵袭、异常骨形成、关节软骨细胞的凋亡、细胞外基质代谢失衡等病理机制。独活寄生汤还可能通过调控新陈代谢通路、环磷酸鸟苷酸-G激酶信号通路等通路分别治疗RA和OA。[结论] 独活寄生汤可祛风除湿、通利关节、补益肝肾、调养气血以“同治”RA、OA等“异病”，其作用机制与调控类风湿关节炎、骨关节炎两者的共同信号通路有关。

Abstract:

[Objective] To explore the mechanism of Duhuo Jisheng Decoction for "treating different diseases with same method" of rheumatoid arthritis (RA) and osteoarthritis (OA) from the perspective of target and biological pathway by means of network pharmacology.[Methods] TCMSP,BATMAN-TCM,UniProt and GeneCards databases were used to predict targets of Duhuo Jisheng Decoction in the treatment of RA and OA. The online tool Venny was used to obtain the common targets,and then the STRING database was used to construct the protein-protein interaction Network among the common targets. The Cytoscape software was used to draw the mechanism Network of the "treating different diseases with same method" by the Duhuo Jisheng Decoction for RA and OA,and the Network Analyzer plug-in and MCODE plug-in were used for topology analysis and cluster analysis respectively. The DAVID database was used for enrichment analysis of biological processes and pathways.[Results] There were 194 targets in total for the treatment of Duhuo Jisheng Decoction on RA and OA,with 80 and 28 specific targets respectively. The modular analysis of the common targets yielded 5 modules,the main modules participated in 10 main related signal pathways,which can be reflected in the proliferation and invasion of synovial cells,pathological mechanisms such as abnormal bone formation,apoptosis of articular cartilage cells,and imbalance of extracellular matrix metabolism. Duhuo Jisheng Decoction may also treat RA and OA by regulating metabolic pathways and cGMP-PKG signaling pathways,respectively.[Conclusion] Duhuo Jisheng Decoction can expel wind and dampness,tonic joints,nourish the liver and kidney,regulate qi and blood to "tongzhi" rheumatoid arthritis,osteoarthritis and other "different diseases". Its mechanism of action is related to the common signal pathway that regulates RA and OA.