JAK2抑制剂AG490对EAE小鼠C57BL/6的Th17/Treg细胞平衡的影响

The effects of AG490 on balance of Th17 / Treg in C57BL /6 EAE mice

目的探讨AG490对EAE小鼠Th17/Treg平衡的影响及其治疗作用。方法以MOG33-35多肽免疫C57BL/6小鼠建立EAE模型,观察AG490干预前后EAE组、AG490组和对照组小鼠脊髓组织炎性细胞浸润情况及p-STAT5、Foxp3和IL-17免疫组化染色阳性细胞数目。结果 AG490组较EAE组小鼠炎症细胞浸润及IL-17阳性细胞数目减少(P<0.05),AG490组小鼠p-STAT5和Foxp3阳性细胞数目较EAE组增多(P<0.05),两组小鼠发病高峰期较发病初期炎症细胞浸润及IL-17阳性细胞数目增多,而p-STAT5和Foxp3阳性细胞数目减少(P<0.05)。结论 (1)AG490通过抑制JAK2-STAT3信号通路抑制炎症反应和免疫应答;(2)JAK2抑制剂可以通过JAK2-STAT3信号通路调节Th17/Treg细胞平衡。

Objective To investigate the effects of a JAK2-STAT3 pathway inhibitor AG490,as a new therapy to MS,on Th17 / Treg balance of MS. Methods The EAE mice established via immunization with MOG33-35 to the C57 BL /6 mice were interfered with AG490 randomly. Observe the pathological change and inflammatory cells of EAE group,AG490 group and control group by HE dyeing,then assess the positive cells of p-STAT5,Foxp3 and IL-17. All indicator of different phase（ initial and acute stage） were compared. Results The inflammatory cells and IL-17 positive cells increased in EAE group（ P〈0. 05）,and they were increased in acute stage than that in initial stage（ P〈0. 05）. The positive cells of p-STAT5 and Foxp3 increased in AG490 group（ P〈0. 05）,and they were decreased in acute stage than that in initial stage（ P〈0. 05）.Conclusion（ 1） AG490 alleviate inflammatory response through inhibiting JAK2-STAT3 pathway.（ 2） JAK2 inhibitor can regulate JAK2-STAT3 pathway to modulate Th17 / Treg balance.