JAK/STAT信号通路在大鼠类风湿关节炎模型发病过程中的表达

Expression of JAK/STAT signal pathway in collagen-induced rat rheumatoid arthritis

目的探讨JAK/STAT信号通路在大鼠类风湿关节炎(RA)发病过程中的表达及意义。方法48只雄性Wistar大鼠随机分为6组,对照组8只,其余均建立胶原诱导的关节炎(CIA)模型,分别在致敏后2、3、4、5、6周分批处死,应用苏木素-伊红(HE)染色、免疫组织化学及免疫印迹法检测发病不同时期滑膜组织的病理变化及p-STAT1、p-STAT3的表达。结果致敏后2周大鼠出现关节炎表现,HE染色可见滑膜组织增生及炎性细胞浸润;第4周关节肿胀达到高峰,病理显示典型血管翳形成;第6周部分软骨及骨组织受到破坏。在CIA发病过程中STAT1、STAT3均处于激活状态,与对照组比较差异有统计学意义(P<0.05)。但二者表达存在时间上的差异,STAT3处于持续激活状态,而STAT1的激活只局限在疾病的中晚期。结论JAK/STAT信号通路参与了CIA的病理过程,针对性阻断JAK/STAT通路可能达到改善RA病理过程的目的。

Objective To explore the dynamic change and meaning of JAK/STAT signal path in the invasive course of collagen-induced arthritis （CIA）. Methods Forty-eight rats were divided into 6 groups randomly, eight rats served as the control group, the rest were for the development of CIA models. Rats were sacrificed at the 2nd, 3rd, 4th, 5th and 6th week after the initial immunity respectively. Then HE staining, immunohistochemistry and immunoblotting were used to detect the pathological changes of synovium in different st ages and the expression of p-STAT1 and p-STAT3. Results On the second week after initial immunity, the rats had arthritis, and the inflammation achieved its peak at the 4th week, then gradually relieved, and a few joints developed rigidity, synovium hyperplasia and inflammatory cell infiltration could be seen at the second week of initial immunity, and pannus could be seen at the 4th week as well as cartilage destroy at the 6th week by HE staining. In the invasive course of CIA, STAT1 and STAT3 were all in activated state detected by immunohistochemistry and immunoblotting, which were significantly different from those of control group and they had a positive correlation with arthritis index, the Pearson＇s value of them were 0.798 and 0.873 respectively. However, there was some difference on time. STAT3 kept at activated state and had positive correlation with pathology score of synovium, and the Pearson＇s value was 0.622. On the contrary, the activation of STAT1 was obviously delayed and only confined to the middle and advanced stage of the disease. Conclusion JAK/STAT signal pathway participates the pathological course of CIA, and blocking the different point of JAK/STAT pathway＇ activation process may reach the goal of reversing the RA＇s pathological course.