骨痨愈康丸通过JAK3/STAT3信号通路对佐剂性关节炎大鼠炎症反应的影响
Effects of Gulao Yukang Pills on inflammatory response in adjuvant arthritis rats through JAK3/STAT3 signaling pathway
  
DOI:10.3969/j.issn.1006-7108.2023.02.011
中文关键词:  类风湿关节炎  骨痨愈康丸  JAK3/STAT3信号通路  调控机制
英文关键词:rheumatoid arthritis  Gulao Yukang Pills  JAK3/STAT3 signaling pathway  regulatory mechanism
基金项目:国家自然科学基金项目(81960832);甘肃中医药大学研究生创新基金资助项目(2022CX26)
作者单位
李金益[1] 宋敏1,2* 田杰祥1,2 王凯1 范凯1 1.甘肃中医药大学中医临床学院,甘肃 兰州 730000 2.甘肃中医药大学附属医院骨科,甘肃 兰州 730000 
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中文摘要:
      目的 基于JAK3/STAT3信号通路探讨骨痨愈康丸对类风湿关节炎模型大鼠的影响机制。方法 将60只Wistar大鼠,随机分为正常对照(Control)组、模型(CIA)组、骨痨愈康丸(GL)组、骨痨愈康丸+JAK受体酪氨酸激酶抑制剂AG490(GL+AG490)组、JAK受体酪氨酸激酶抑制剂AG490(AG490)组,除正常对照组外,其余四组均建立胶原诱导性类风湿关节炎(CIA)大鼠模型。通过ELISA法检测血清中TNF-α、IL-6、IL-17水平,运用免疫组化法与实时荧光定量聚合酶链式反应(real-time PCR)检测踝关节软骨和滑膜组织中JAK3、STAT3蛋白及mRNA的表达情况。结果 与Control组比较,CIA、GL、GL+AG490、AG490组大鼠踝关节肿胀明显,伴关节畸形、大鼠活动明显减少、跛行、毛色暗淡无光泽、体重减轻;模型大鼠血清中TNF-α、IL-6、IL-17水平显著升高;JAK3、STAT3蛋白表达显著升高(P<0. 05)。与CIA组相比,各治疗组大鼠血清中TNF-α、IL-6、IL-17水平降低;JAK3、STAT3蛋白及mRNA表达下调(P<0. 05)。结论 骨痨愈康丸能减轻RA的炎症反应,其作用机制可能与抑制JAK3/STAT3信号通路及其下游基因蛋白表达有关。
英文摘要:
      Objective To explore the mechanism of Gulao Yukang Pills on rheumatoid arthritis model rats based on JAK3/STAT3 signaling pathway. Methods 60 Wistar rats were randomly divided into normal control (Control) group, model (CIA) group, Gulao Yukang Pills (GL) group, Gulao Yukang Pills+JAK receptor tyrosine kinase inhibitor AG490 (GL+AG490) group, and JAK receptor tyrosine kinase inhibitor AG490 (GL+AG490) group. In the AG490 (AG490) group, an amino-kinase inhibitor, except the normal control group, the other 4 groups established collagen-induced rheumatoid arthritis (CIA) rat models. The levels of TNF-α, IL-6 and IL-17 in serum were detected by ELISA, and the proteins of JAK3 and STAT3 in ankle cartilage and synovial tissue were detected by immunohistochemistry and real-time PCR. Results Compared with the Control group, the ankle joints of the CIA group, GL group, GL+AG490 group and AG490 group were significantly swollen, accompanied by joint deformity, the activity of the rats was significantly reduced, lameness, dull hair color, and weight loss; The levels of TNF-α, IL-6 and IL-17 were significantly increased; the protein expressions of JAK3 and STAT3 were significantly increased (P<0.05). Compared with the CIA group, the levels of TNF-α, IL-6 and IL-17 in the serum of the rats in each treatment group were decreased; the protein and mRNA expressions of JAK3 and STAT3 were down-regulated (P<0.05). Conclusion Gulao Yukang Pills can reduce the inflammatory response of RA, and its mechanism of action may be related to the inhibition of JAK3/STAT3 signaling pathway and its downstream gene protein expression.
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