蒙药三子汤治疗类风湿关节炎的药效学及网络药理学研究  

Pharmacodynamics and Network Pharmacology Study of Mongolian Medicine Sanzi Decoction in the Treatment of Rheumatoid Arthritis

作　　者：赵子龙[1] 石慧 杨夏[1] ZHAO Zilong;SHI Hui;YANG Xia(Baogang Hospital of Inner Mongolia,Baotou 014010,China)

机构地区：[1]内蒙古包钢医院,内蒙古包头014010

出　　处：《西部中医药》2024年第9期1-6,共6页Western Journal of Traditional Chinese Medicine

基　　金：内蒙古自治区自然科学基金(2018MS03078)。

摘　　要：目的:探讨蒙药三子汤对胶原诱导关节炎模型(collagen induced arthritis,CIA)小鼠关节的保护作用及其治疗类风湿关节炎(rheumatoid arthritis,RA)的作用机制。方法:以CIA小鼠为研究对象,通过关节炎指数评分及关节病理改变观察三子汤对CIA小鼠关节的保护作用。通过中药系统药理学数据库和分析平台(traditional Chinese medicines systems pharmacology platform,TCMSP)、Swiss Target Prediction数据库及DisGeNET数据库筛选得到三子汤治疗RA的潜在靶点;应用STRING数据库对潜在靶点进行蛋白-蛋白相互作用分析;应用DAVID数据库对靶点进行基因本体(gene ontology,GO)和京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)富集分析;采用CytoHubba插件进行Hub节点筛选。结果:与模型组比较,三子汤组小鼠关节炎指数评分降低(P<0.05),关节滑膜增生、软骨侵蚀等明显缓解。共筛选得到三子汤活性成分32个,靶点629个,RA疾病靶点1317个,三子汤治疗RA潜在靶点171个;GO及KEGG分析结果显示靶点参与多种与RA相关的功能、生物过程及信号通路;Hub节点筛选明确三子汤治疗RA的关键信号通路为磷脂酰肌醇3激酶-蛋白激酶B(phosphatidylinositol 3 kinase-protein kinase B,PI3K-Akt)、丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)、Ras信号通路,关键靶点为双重特异性促分裂原活化蛋白激酶激酶1(dual specificity mitogen-activated protein kinase kinase 1,MAP2K1)、RAF原癌基因丝氨酸/苏氨酸蛋白激酶(RAF proto-oncogene serine/threonine-protein kinase,RAF1)、MAPK3。结论:蒙药三子汤可缓解CIA小鼠疾病进展;网络药理学分析三子汤可能作用于MAP2K1、MAPK3及其他关键靶点,调节PI3K-Akt、MAPK等信号通路,发挥关节保护作用。Objective:To discuss the protective effects of Mongolian medicine Sanzi decoction on the joint in the mice with collagen induced arthritis(CIA)and its mechanism of treating rheumatoid arthritis(RA).Methods:CIA mice were chosen as the subjects of the study,arthritis index scores and pathological changes of the joints were applied to observe the protection effects of Sanzi decoction on the joints in CIA mice.The potential targets of Sanzi decoction in the treatment of RA were searched from TCMSP,Swiss Target Prediction and DisGeNET database;protein-protein interaction(PPI)of the potential targets was analyzed using STRING database;GO and KEGG enrichment analysis of the targets were performed using DAVID database;Hub node filtering was conducted using CytoHubba plug-in components.Results:Compared with the model group,arthritis index scores reduced in the mice of Sanzi decoction group(P<0.05),synovial membrane hyperplasia and cartilage erosion in joints was significantly relieved.The study has obtained 32 active ingredients of Sanzi decoction,629 targets,1317 RA disease targets and 171 potential targets of the decoction in the treatment of RA;GO and KEGG results showed that the target is involved in a variety of functions,biological processes and signaling pathways associated with RA;Hub node screening clarified that the key signaling pathways in the treatment of RA by Sanzi decoction were PI3K-Akt,MAPK and Ras signaling pathway,and the key targets were MAP2K1,RAF1 and MAPK3.Conclusion:Mongolian medicine Sanzi decoction could relieve disease progression in CIA mice;network pharmacology prediction presents that the decoction could protect the joint possibly by acting on the key targets including MAP2K1,MAPK3 and others,and regulating the signaling pathways such as PI3K-Akt,and MAPK.

关 键 词：类风湿关节炎 网络药理学 蒙药 三子汤 小鼠 

分 类 号：R29[医药卫生—民族医学]