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中国临床药理学与治疗学 ›› 2024, Vol. 29 ›› Issue (1): 26-36.doi: 10.12092/j.issn.1009-2501.2024.01.003

• 基础研究 • 上一篇    下一篇

益气养阴通络方对类风湿关节炎的作用分析及验证

关 蕊1,姚家树2,赵夜雨2,郑建南2,齐 庆2,于 静2,高明利2   

  1. 1辽宁中医药大学,沈阳  110847,辽宁;2辽宁中医药大学附属医院风湿科,沈阳  110032,辽宁

  • 收稿日期:2023-07-13 修回日期:2023-09-08 出版日期:2024-01-26 发布日期:2024-01-15
  • 通讯作者: 高明利,男,硕士,主任医师,博士生导师,研究方向:中医药治疗风湿病的临床研究。 E-mail: gmllnzy@139.com
  • 作者简介:关蕊,女,博士研究生,主治医师,研究方向:中医药治疗风湿病的临床研究。 E-mail: vivian-gr@outlook.com
  • 基金资助:
    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)

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

GUAN Rui1, YAO Jiashu2, ZHAO Yeyu2, ZHENG Jiannan2, QI Qing2, YU Jing2, GAO Mingli2   

  1. 1 Liaoning University of Traditional Chinese Medicine, Shenyang 110847, Liaoning, China; 2 Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang 110032, Liaoning, China
  • Received:2023-07-13 Revised:2023-09-08 Online:2024-01-26 Published:2024-01-15

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。

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

Abstract:

AIM: Yi Qi Yang Yin Decoction (YQYY) has been used to treat patients with rheumatoid arthritis (RA) and achieved good results in clinical applications, but the mechanism still needs to be explored. The purpose was to investigate the mechanism of YQYY in rats with collagen-induced arthritis. METHODS: The possible treatment target and signaling pathway were predicted by bioinformatics and network pharmacology analysis. Elisa,quantitative real-time polymerase chain reaction, and Western Blot were used to verify the mechanism of YQYY in treating RA. RESULTS: FABP4, MMP9 and PTGS2 were the most common predicational therapeutic targets. The results of pathology and CT showed that YQYY could improve ankle swelling, synovitis and bone erosion in CIA rats. Compared with the model group, YQYY or YQYY+MTX can significantly reduce the secretion of CRP, TNF-α, IL-1β and 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 increased (P<0.01). YQYY could significantly reduce the expression of FABP4, IKKα and pp65 proteins in synovium, and suppress the activate of NF-κB signaling 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 provided experimental evidence for the efficacy of YQYY decoction in clinical practice.

Key words: YQYY decoction, rheumatoid arthritis, bioinformatics, network pharmacology

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