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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
                    1*
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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
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