基于JAK2/STAT3信号通路探讨通痹胶囊治疗类风湿关节炎的作用机制

Mechanism of Tongbi capsules for rheumatoid arthritis on JAK2/STAT3 signaling pathway

目的观察通痹胶囊对佐剂性关节炎(AA)大鼠JAK2/STAT3信号通路及相关炎性因子的影响。方法以弗氏完全佐剂制备大鼠AA模型,通痹胶囊(375、750、1500 mg·kg-1)灌胃治疗,HE染色观察组织病理形态学变化;酶联免疫吸附(ELISA)法检测大鼠血清及滑膜中白细胞介素-6(IL-6)、γ干扰素(IFN-γ)的表达水平;蛋白免疫印迹(Western blot)法检测大鼠滑膜组织中p-JAK2、JAK2、p-STAT3、STAT3的蛋白表达。结果与正常组相比,造模后大鼠血清及滑膜组织中IL-6、IFN-γ含量明显升高,p-JAK2/JAK2、p-STAT3/STAT3相对表达显著增多(P<0.01);与模型组相比,通痹胶囊能够有效降低大鼠血清及滑膜组织中IL-6、IFN-γ的含量,并抑制滑膜组织中JAK2、STAT3蛋白磷酸化(P<0.01)。结论通痹胶囊具有明显的抗炎作用,其治疗类风湿关节炎作用机制之一可能为抑制JAK2/STAT3信号通路的激活。

Objective To observe the effect of Tongbi capsules on JAK2/STAT3 signaling pathway and related inflammatory factors in rats with adjuvant arthritis.Methods Adjuvant arthritis rat models were prepared with Freund’s complete adjuvant.Tongbi capsules (375,750,and 1500 mg·kg-~1) were administered by gavage.Histopathological changes were observed by HE staining.The expression levels of interleukin-6 (IL-6) and IFN-γ in the serum and the synovium of rats were detected by ELISA.Western blot was used to detect the protein expressions of p-JAK2,JAK2,p-STAT3 and STAT3 in the synovial tissue of rats.Results Compared with the normal group,the levels of IL-6 and IFN-γ were significantly increased in the serum and the synovial tissue of rats after modeling,and the relative expressions of p-JAK2/JAK2 and p-STAT3/STAT3 were significantly raised (P<0.01).Compared with the model group,Tongbi capsules effectively reduced the content of IL-6 and IFN-γ in the serum and the synovial tissue of the rats,and inhibited the phosphorylation of JAK2 and STAT3 proteins in the synovial tissue (P <0.01).Conclusion Tongbi capsules have obvious anti-inflammatory effect,and its potential mechanism in treating rheumatoid arthritis may be the inhibition of activation of the JAK2/STAT3 signaling pathway.