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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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呼格吉乐 ,王青虎 ,张小峰 ,康秀荣 ,白迎春 ,李胡日查 ,高明霞(1.内蒙古民族大学蒙医药学院,内蒙古
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通辽 028000;2.通辽职业学院药品食品系,内蒙古 通辽 028000)
中图分类号 R965;R285 文献标志码 A 文章编号 1001-0408(2025)13-1604-06
DOI 10.6039/j.issn.1001-0408.2025.13.09
摘 要 目的 基于分化簇 4(CD4)/淋巴细胞特异性酪氨酸激酶(LCK)/70 kDa 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、21.6 mg/kg)以及阳性对照组(雷公藤多苷片,6.3 mg/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 28 d。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。
关键词 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
Study on mechanism of the effective substance groups from Artemisia ordosica in ameliorating rheumatoid
arthritis
Hugejile ,WANG Qinghu ,ZHANG Xiaofeng ,KANG Xiurong ,BAI Yingchun ,Lihuricha ,GAO Mingxia 1
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(1. College of Traditional Mongolian Medicine, Inner Mongolia University for Nationalities, Inner Mongolia
Tongliao 028000, China;2. Department of Medicine and Food, Tongliao Vocational College, Inner Mongolia
Tongliao 028000, China)
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,
Δ 基金项目 国家自然科学基金项目(No.82260681);内蒙古自治
区自然科学基金项目(No.2023MS08027);内蒙古自治区教育厅一流 RAR-related orphan receptor γt (RORγt), and forkhead box
学科科研专项项目子课题(No.YLXKZX-NMD-002);蒙药研发国家地 protein 3 (Foxp3) in ankle synovial tissue were determined.
方联合工程研究中心开放课题(No.MDK2024004) RESULTS Compared with normal group, the changes in
*第一作者 博士研究生。研究方向:蒙药有效物质及其药理研
ankle joint swelling, arthritis index, the levels of IL-1β, IL-
究。E-mail:1033814209@qq.com
# 通信作者 教授,博士生导师,博士。研究方向:蒙药有效物质及 21, IL-17A, IL-2, IFN-γ and IL-6 in serum and joint fluid,
其药理研究。E-mail:wqh693@163.com the levels of Th1, Th17 cells and Th17/Treg value in whole
· 1604 · China Pharmacy 2025 Vol. 36 No. 13 中国药房 2025年第36卷第13期