蠲痹汤“异病同治”法治疗类风湿关节炎和强直性脊柱炎的网络药理学作用机制研究

Network Pharmacology-based Study on the Mechanism of Treating Rheumatoid Arthritis and Ankylosing Spondylitis with Juanbi Decoction Based on"Treating Different Diseases with Same Method"

目的:通过网络药理学原理探讨蠲痹汤“异病同治”法治疗类风湿关节炎和强直性脊柱炎的潜在作用机制。方法:在中药系统药理学数据库平台检索蠲痹汤的活性成分并预测其潜在靶点,借助Cytoscape 3.7.2软件构建药物成分与靶点之间的网络图;通过疾病相关数据库平台检索类风湿关节炎和强直性脊柱炎的疾病靶点,利用Venny在线工具构建药物与疾病的关键靶点Venny图。基于STRING数据库构建蛋白间PPI网络图,然后按Dgree值大于平均值进一步筛选核心靶点;运用DAVID数据库,对基因本体及基因组百科全书通路富集进行分析。结果:经过筛选得到蠲痹汤有效活性成分153个,潜在作用靶点137个,经疾病数据库获得强直性脊柱炎靶点188个,类风湿关节炎靶点729个,映射靶点23个,根据Dgree≥11筛选到10个核心靶点作用于一氧化氮生物合成过程的正调控、细胞因子活性、细胞对脂多糖的反应等119项生物过程及TNF信号通路、NOD样受体通路、Toll样受体通路、HIF-1信号通路等32条相关生物通路,进而调节体内炎症反应及氧化应激水平。结论:依据网络药理学相关技术方法能够较为科学的从分子水平层面揭示蠲痹汤“异病同治”类风湿关节炎和强直性脊柱炎的潜在作用机制,为进一步的临床应用和实验验证提供理论基础与依据。

Objective:To explore the potential mechanism of treating rheumatoid arthritis and ankylosing spondylitis with Juanbi decoction on the foundation of"treating different diseases with same method"through the principle of network pharmacology.Methods:The active ingredients of Juanbi decoction were searched from Traditional Chinese Medicine System Pharmacology Database Platform(TCMSP)to predict the potential targets,a network diagram between the ingredients of the drugs and the targets was constructed via Cytoscape 3.7.2 software;the targets of rheumatoid arthritis and ankylosing spondylitis were retrieved by disease-related database platform,Venny diagram of key targets of drugs and diseases was constructed utilizing Venny online tools.PPI network diagram between proteins was built based on the STRING database,and then the core targets were further screened according to the Dgree value greater than the average value;gene ontology(GO)and genome encyclopedia(KEGG)were analyzed using DAVID database.Results:Through screening,there are 153 active ingredients and 137 potential action targets from Juanbi decoction,188 targets related to ankylosing spondylitis,729 targets of rheumatoid arthritis and 23 mapping targets were obtained via disease database,ten core targets were screened according to Dgree≥11,acting on 119 biological processes including positive regulation of nitric oxide biosynthesis,the activity of cytokine,cell response to lipopolysaccharide,and 32 associated biological pathways containing TNF signal pathway,NOD-like receptor pathway,Toll-like receptor pathway and HIF-1 signal pathway,thereby regulating human inflammatory response and oxidative stress levels in vivo.Conclusion:The potential mechanism of Juanbi decoction in the treatment of rheumatoid arthritis and ankylosing spondylitis on the foundation of"treating different diseases with same method"is revealed in a scientific way from molecular level through the related technology and methods of network pharmacology,which could produce theoretical foundation and reference for further clinical application and experimental verification.