黑沙蒿有效物质群改善类风湿性关节炎的作用机制研究
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篇名: | 黑沙蒿有效物质群改善类风湿性关节炎的作用机制研究 |
TITLE: | Study on mechanism of the effective substance groups from Artemisia ordosica in ameliorating rheumatoid arthritis |
摘要: | 目的 基于分化簇4(CD4)/淋巴细胞特异性酪氨酸激酶(LCK)/70kDa链相关蛋白激酶(ZAP70)/白细胞介素17(IL-17)信号通路研究黑沙蒿有效物质群(简称HSH)对类风湿性关节炎(RA)的改善作用及机制。方法将大鼠分为正常组、模型组和HSH低、中、高剂量组(2.7、10.8、21.6mg/kg)以及阳性对照组(雷公藤多苷片,6.3mg/kg),每组10只。除正常组外,其余各组大鼠采用完全弗氏佐剂诱导RA模型。造模成功后,各组大鼠灌胃相应药物或生理盐水,每天1次,连续28d。检测大鼠踝关节肿胀度、关节炎指数;观察大鼠踝关节组织病理形态学;检测大鼠血清和关节液中炎症因子[IL-1β、IL-21、IL-17A、IL-2、γ干扰素(IFN-γ)和IL-6]水平,大鼠全血及脾脏中Th1、Th17、Treg细胞水平,大鼠踝关节滑膜中LCK、原癌基因酪氨酸蛋白激酶Fyn、ZAP70、CD45、视黄酸受体相关孤儿受体γt亚型(RORγt)、叉头框蛋白3(Foxp3)的蛋白和mRNA表达水平。结果与正常组比较,模型组大鼠踝关节肿胀度,关节炎指数,血清和关节液中IL-1β、IL-21、IL-17A、IL-2、IFN-γ、IL-6水平,全血和脾脏中Th1、Th17细胞水平以及Th17/Treg值,踝关节滑膜中LCK、Fyn、ZAP70、CD45、RORγt蛋白和mRNA表达水平均显著增加/升高(P<0.05);脾脏中Treg细胞水平、踝关节滑膜中Foxp3蛋白和mRNA表达水平均显著降低(P<0.05)。与模型组比较,阳性对照组和HSH各剂量组上述大部分指标水平显著逆转(P<0.05),踝关节组织病变程度明显改善、炎症减轻。结论HSH可通过调节T细胞受体信号通路中CD4/LCK/ZAP70/IL-17途径的级联反应,调节Th17/Treg平衡,从而抑制RA大鼠的炎症反应,减轻滑膜组织损伤。 |
ABSTRACT: | OBJECTIVE To investigate the ameliorating effect and mechanism of the effective substance groups from Artemisia ordosica(Abbreviated as HSH) on rheumatoid arthritis (RA) based on cluster of differentiation 4/lymphocyte cell-specific protein- tyrosine kinase/zeta-chain-associated protein kinase of 70 kDa/interleukin-17(CD4/LCK/ZAP70/IL-17) signaling pathway. METHODS The rats were divided into normal group, model group, HSH low-dose, medium-dose and high-dose groups (2.7, 10.8, 21.6 mg/kg) and positive control group (Tripterygium glycosides tablet, 6.3 mg/kg), with 10 rats in each group. Except for normal group, RA rat model was induced by complete Freund’s adjuvant in other groups. After modeling, each group was given relevant medicine or normal saline intragastrically, once a day, for 28 consecutive days. The changes in ankle joint swelling and arthritis index in rats were determined; the pathological changes of ankle joint tissue were observed; the levels of inflammatory factors [IL-1β, IL-21, IL-17A, IL-2, interferon-γ (IFN-γ) and IL-6] in serum and joint fluid of rats were determined; the levels of Th1, Th17 and Treg cells in the whole blood and spleen of rats were detected; protein and mRNA expressions of LCK, proto-oncogene tyrosine-protein kinase Fyn (Fyn), ZAP70, CD45, RAR-related orphan receptor γt (RORγt), and forkhead box protein 3 (Foxp3) in ankle synovial tissue were determined. RESULTS Compared with normal group, the changes in ankle joint swelling, arthritis index, the levels of IL-1β, IL-21, IL-17A, IL-2, IFN-γ and IL-6 in serum and joint fluid, the levels of Th1, Th17 cells and Th17/Treg value in whole blood and spleen, and the protein and mRNA expression levels of LCK, Fyn, ZAP70, CD45, and RORγt in ankle joint synovium were all significantly increased/elevated (P<0.05). The level of Treg cells in the spleen, as well as the protein and mRNA expression levels of Foxp3 in the ankle joint synovium were significantly decreased (P<0.05). Compared with model group, most of the above-mentioned indicators were significantly reversed in the positive control group and all dose groups of HSH (P<0.05). The degree of pathological changes in ankle joint tissues was markedly improved, and inflammation was alleviated. CONCLUSIONS HSH can regulate the cascade reactions in the CD4/LCK/ZAP70/IL-17 pathway within the T-cell receptor signaling pathway, thereby modulating the Th17/Treg balance. This leads to the suppression of inflammatory responses and the alleviation of synovial tissue damage in rats with RA. |
期刊: | 2025年第36卷第13期 |
作者: | 呼格吉乐;王青虎;张小峰;康秀荣;白迎春;李胡日查;高明霞 |
AUTHORS: | Hugejile ,WANG Qinghu,ZHANG Xiaofeng,KANG Xiurong,BAI Yingchun,Lihuricha,GAO Mingxia |
关键字: | 黑沙蒿;有效物质群;类风湿性关节炎;CD4/LCK/ZAP70/IL-17信号通路;Th17/Treg平衡;炎症反应 |
KEYWORDS: | Artemisia ordosica; effective substance groups; rheumatoid arthritis; CD4/LCK/ZAP70/IL-17 signaling pathway; |
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