益气养阴通络方对类风湿关节炎的作用分析及验证OA北大核心CSTPCD
Analysis and verification of the effect of Yi Qi Yang Yin decoction on rheumatoid arthritis
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,IKKα and p65 in synovial tissue(P<0.01),PPARγ was in-creased(P<0.01).YQYY could significantly reduce the expression of FABP4,IKKa and 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.
关蕊;姚家树;赵夜雨;郑建南;齐庆;于静;高明利
辽宁中医药大学,沈阳 110847,辽宁辽宁中医药大学附属医院风湿科,沈阳 110032,辽宁
药学
益气养阴通络方类风湿关节炎生物信息学网络药理学
YQYY decoctionrheumatoid arthri-tisbioinformaticsnetwork pharmacology
《中国临床药理学与治疗学》 2024 (001)
26-36 / 11
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)
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