中国骨质疏松杂志

由JAK2/STAT3探讨益气蠲痹方治疗类风湿关节滑膜炎作用机制

To explore the mechanism of Yiqi Juanbi Formula in the treatment of rheumatoid arthritis synovitis based on the JAK2/STAT3

DOI：10.3969/j.issn.1006-7108.2025.08.002

中文关键词: 益气蠲痹方类风湿关节炎滑膜炎症 Janus激酶2/信号转导与转录激活因子3信号通路

英文关键词:Yiqi Juanbi Formula rheumatoid arthritis synovial inflammation JAK2/STAT 3signaling pathway

基金项目:国家自然科学基金（82460945）；省中医药科研项目（GZKP-2022-7）；兰州市指导性计划项目（2023-ZD-39）

作者	单位
康惠琴1 李浩林1 李伟青2* 杨彩红1 崔馨予1 贺佩鑫1 程伟刚1 王海东2	1．甘肃中医药大学，甘肃兰州 730000 2．甘肃省中医院风湿骨病中心，甘肃兰州 730050

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中文摘要:

目的研究益气蠲痹方通过调节Janus激酶2/信号转导与转录激活因子3信号通路（JAK2/STAT3）对类风湿关节炎大鼠（CIA）滑膜炎症的作用机制。方法实验选用 SD 大鼠，随机均分为七组，分别为空白组、模型组、甲氨蝶呤组、雷公藤多苷片组，以及益气蠲痹方低、中、高剂量组。每7 d观察大鼠关节炎指数及关节肿胀程度；通过苏木素-伊红（HE）染色观察踝关节组织；采用酶联免疫吸附测定法（ELISA）对血清白细胞介素 6（IL - 6）、白细胞介素 1β（IL - 1β）、肿瘤坏死因子 α（TNF - α）及 γ 干扰素（INF - γ）予以检测；实时荧光定量多聚核苷酸链反应（qRT-PCR)和蛋白免疫印迹法（Western Blot）检测Janus激酶2（JAK2）、信号转导和转录激活因子3（STAT3）、细胞因子信号抑制因子1（SOCS1）和 3（SOCS3）的m RNA及蛋白表达；运用免疫组化法检测基质金属蛋白酶9（MMP-9）和13（MMP-13）。结果甲氨蝶呤组、益气蠲痹方高剂量组和雷公藤多苷片组降低血清IL-6、IL-1β、TNF-α、INF-γ水平（P<0.05，P<0.01）; 雷公藤多苷片组和益气蠲痹方中、高剂量组降低JAK2、STAT3 mRNA及蛋白表达（P<0.05，P<0.01），升高SOCS1和SOCS3 m RNA及蛋白表达（P<0.05，P<0.01）；甲氨蝶呤组、雷公藤多苷片组及益气蠲痹方中、高剂量组降低MMP-9、MMP-13蛋白阳性表达面积（P<0.05，P<0.01），缓解滑膜细胞增生，降低炎性细胞浸润。结论益气蠲痹方通过抑制JAK2/STAT3信号通路的激活，改善关节炎症环境、抑制滑膜增生，达到治疗类风湿关节炎的目的。

英文摘要:

Objective To explore the mechanism by which the Yiqi Juanbi Formula modulates the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway in relation to synovial inflammation in rats with rheumatoid arthritis (CIA). Methods The experiment used SD rats, which were randomly divided into 7 groups, including a blank group, a model group, a methotrexate group, a triptolide tablets group, and low, medium, and high-dose groups of the Qi Gui Ming decoction. The arthritis index and degree of joint swelling were observed every 7 days; hematoxylin and eosin (HE) staining was used to observe the tissue of the ankle joint; enzyme-linked immunosorbent assay (ELISA) was used to detect serum interleukin 6 (IL-6), interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α), and gamma interferon (INF-γ); real-time quantitative polymerase chain reaction (qRT-PCR) and protein immunoblotting (Western Blot) were used to detect the mRNA and protein expression of Janus kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3), cytokine signal inhibitor 1 (SOCS1), and 3 (SOCS3); immunohistochemistry was used to detect matrix metalloproteinase 9 (MMP-9) and 13 (MMP-13) . Results The methotrexate group, the high-dose group of the Yiqi Juanbi Formula, and the tripterygium glycosides tablet group decreased the levels of serum IL-6, IL-1β, TNF-α, and INF-γ (P<0.05, P<0.01); the tripterygium glycosides tablet group and the medium and high-dose groups of the Yiqi Juanbi Formula decreased the mRNA and protein expressions of JAK2 and STAT3 (P<0.05, P<0.01), and increased the mRNA and protein expressions of SOCS1 and SOCS3 (P<0.05, P<0.01); the methotrexate group, the tripterygium glycosides tablet group, and the medium and high-dose groups of the Yiqi Juanbi Formula decreased the positive expression area of MMP-9 and MMP-13 proteins (P<0.05,P<0.01), alleviated synovial cell proliferation, and reduced inflammatory cell infiltration.Conclusion By inhibiting the activation of JAK2/STAT3 signalling pathway, Yiqi Remission Formula improves the inflammatory environment of joints and inhibits synovial proliferation, achieving the treatment of rheumatoid arthritis.

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