SOCS1-JAK2-STAT3信号通路在C57BL/6小鼠实验性自身免疫性脑脊髓炎模型中作用机制探讨

Investigating mechanism of SOCS1-JAK2-STAT3 pathway in C57BL /6 mice of EAE

目的:探讨SOCS1-JAK2-STAT3通路在C57BL/6小鼠实验性自身免疫性脑脊髓炎(EAE)发病中的作用机制,为多发性硬化(MS)的治疗寻找新的靶点。方法:对比AG490干预组、EAE模型组和空白对照组各组小鼠发病情况,各组发病初期和发病高峰期胸腺组织HE染色,及胸腺中IL-17、RORγt、SOCS1及p-STAT3免疫组化阳性细胞表达。结果:AG490干预组发病时间迟于EAE组(P<0.05),其高峰期神经功能评分显著低于EAE组(P<0.05),AG490干预组胸腺组织中IL-17、RORγt、SOCS1及p-STAT3的表达与EAE组比较明显下降(P<0.05),但各组发病高峰期均较发病初期含量增高(P<0.05)。结论:①AG490可以通过抑制SOCS1-JAK2-STAT3信号通路,降低特异性免疫应答,减少炎症反应。②SOCS1-JAK2-STAT3信号通路在EAE中发挥重要作用,可以作为治疗的新靶点。

Objective：To investigate the mechanism of SOCS1-JAK2-STAT3 pathway in C57BL/6 mice of EAE and detect the new target of treating MS. Methods： The mice were divided into three groups： AG490 group, EAE group and control group. EAE mice were established and some mice were interfered with AG490 randomly. There were two disease phases （initial stage and acute stage ） were observed. The clinical syndrome were assessed first; then pathological change of thymus were observed by HE dyeing ; pos- itive cells of IL-17, RORsyt, SOCS1 and p-STAT3 in thymus were determined by immunohistochemistry. Results： The decreased of morbidity and clinical neurological score were more obvious in AG490 group （ P 〈 0.05 ）. Expression of IL-17, ROR＇yt, SOCS1 and p- STAT3 were lower in AG490 group than in EAE group（ P 〈 0.05 ） , and they were increased in acute stage than in initial stage （P 〈 0.05）. Conclusion ： ①AG490 can alleviate inflammatory response of EAE mice through inhibiting SOCS1-JAK2-STAT3 signal path ; ②SOCS-JAK-STAT signal path play an important role in EAE and could act as a new target of therapy.