益气养阴通络方对类风湿关节炎的作用分析及验证  

Analysis and verification of the effect of Yi Qi Yang Yin decoction on rheumatoid arthritis

作　　者：关蕊[1] 姚家树[2] 赵夜雨[2] 郑建南 齐庆[2] 于静[2] 高明利[2] GUAN Rui;YAO Jiashu;ZHAO Yeyu;ZHENG Jiannan;QI Qing;YU Jing;GAO Mingli(Liaoning University of Traditional Chinese Medicine,Shenyang 110847,Liaoning,China;Affiliated Hospital of Liaoning University of Traditional Chinese Medicine,Shenyang 110032,Liaoning,China)

机构地区：[1]辽宁中医药大学,辽宁沈阳110847 [2]辽宁中医药大学附属医院风湿科,辽宁沈阳110032

出　　处：《中国临床药理学与治疗学》2024年第1期26-36,共11页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：高明利全国名老中医药专家传承工作室建设项目,国中医药人教函【2022】75号;辽宁省自然科学基金项目(2021-BS-180);辽宁省教育厅项目(L202041)。

摘　　要：目的:益气养阴通络(YQYY)方在类风湿关节炎(RA)患者的临床使用中取得良好的效果,本研究目的是为了探究YQYY方对胶原诱导的关节炎(collagen Ⅱ-induced arthritis,CIA)大鼠的作用机制。方法:通过生物信息学、网络药理学,对YQYY方治疗RA的靶点及可能起作用的信号通路进行预测;采用ELISA、qPCR、Western blot法验证YQYY方治疗RA的作用机制。结果:FABP4、MMP9和PTGS2是预测的共同治疗靶点。病理和CT结果显示YQYY方能改善CIA大鼠踝关节肿胀程度、滑膜炎及骨侵蚀。与模型组相比,YQYY组、YQYY+甲氨蝶呤(MTX)组可显著减轻CIA大鼠血清中C反应蛋白(CRP)、TNF-α、IL-1β、FABP4的分泌(P<0.05或P<0.01),并且使滑膜组织中FABP4、IKKα、p65的mRNA表达降低(P<0.01),PPARγ升高(P<0.01)。蛋白电泳结果显示,YQYY方治疗能明显降低FABP4、IKKα、pp65蛋白在滑膜中的表达,抑制NF-κB信号通路的激活。结论:FABP4、MMP9和PTGS2可能是YQYY方治疗RA的靶点;YQYY方能够缓解CIA大鼠滑膜炎,并通过抑制FABP4/PPARγ/NF-κB通路调控炎症反应,从而发挥治疗RA的作用;YQYY方联合应用MTX的疗效更为突出。该研究为临床实践中单独或联合使用YQYY方疗效的有效性提供了实验依据。AIM:Yi Qi Yang Yin Decoction(YQYY)has been used to treat patients with rheumatoid ar-thritis(RA)and achieved good results in clinical ap-plications,but the mechanism still needs to be ex-plored.The purpose was to investigate the mecha-nism of YQYY in rats with collagen-induced arthri-tis.METHODS:The possible treatment target and signaling pathway were predicted by bioinformatics and network pharmacology analysis.Elisa,quantita-tive real-time polymerase chain reaction,and West-ern Blot were used to verify the mechanism of YQYY in treating RA.RESULTS:FABP4,MMP9 and PTGS2 were the most common predicational thera-peutic targets.The results of pathology and CT showed that YQYY could improve ankle swelling,sy-novitis and bone erosion in CIA rats.Compared with the model group,YQYY or YQYY+MTX can sig-nificantly reduce the secretion of CRP,TNF-α,IL-1βand FABP4 in serum of CIA rats(P<0.05 or P<0.01),meanwhile,reduce the mRNA of FABP4,IKKαand p65 in synovial tissue(P<0.01),PPARγwas in-creased(P<0.01).YQYY could significantly reduce the expression of FABP4,IKKαand pp65 proteins in synovium,and suppress the activate of NF-κB sig-naling pathway.CONCLUSION:FABP4,MMP9 and PTGS2 may be the targets of YQYY decoction for RA treatment.YQYY can relieve joint symptoms in CIA rats,and regulate inflammation by inhibiting FABP4/PPARγ/NF-κB signaling pathway,playing a role in the treatment of RA.The effect of YQYY combined with MTX was more prominent.This pro-vided experimental evidence for the efficacy of YQYY decoction in clinical practice.

关 键 词：益气养阴通络方 类风湿关节炎 生物信息学 网络药理学 

分 类 号：R965.2[医药卫生—药理学]