干扰素调节因子4介导治疗性亚低温在缺血性脑卒中小鼠中的神经保护作用机制

Neuroprotective mechanism of interferon regulatory factor 4 mediating therapeutic hypothermia in mice with ischemic stroke

目的:探讨干扰素调节因子4(IRF4)介导治疗性亚低温(TH)在小鼠缺血性脑卒中(IS)的作用机制。方法:分别对野生型和IRF4基因敲除型IS小鼠开展TH。TH结束后,分别检测缺血半暗带脑组织中促炎细胞因子与抗炎细胞因子,M1、M2型巨噬细胞标志物以及IRF4的表达水平。随后进行神经功能测试,利用TTC染色检测小鼠脑梗死体积,同时免疫荧光染色检测细胞凋亡。结果:TH显著减少IS小鼠脑梗死体积并改善神经功能;IRF4基因敲除致使TH的保护作用消失:TH并未减少IRF4基因敲除IS小鼠脑梗死体积,亦未改善其神经功能。结论:TH可能通过上调IRF4表达,调控巨噬细胞极化和炎症细胞因子表达水平,最终发挥抗炎和脑保护作用。

Objective:To explore the effect and mechanism of interferon regulatory factor 4(IRF4)mediating therapeutic hypothermia(TH)on ischemic stroke(IS)in mice.Methods:TH was performed on wild⁃type and IRF4 knockout⁃type IS mice.After TH,the expression levels of pro⁃inflammatory cytokines and anti⁃inflammatory cytokines,M1 and M2 macrophage markers,and IRF4 in ischemic penumbra brain tis⁃sue were detected.Neural function was tested,the cerebral infarction volume was calculated after TTC staining,and the apoptosis was assayed with immunofluorescent staining.Results:TH significantly re⁃duced cerebral infarction volume and improved neurological function of IS mice.IRF4 knockout elimi⁃nated the protective effect of TH:TH neither reduced the volume of cerebral infarction nor improved the neurological function of IRF4 knockout IS mice.Conclusion:TH may regulate the macrophage polariza⁃tion and expression of inflammatory cytokines through up⁃regulating the expression of IRF4 and finally exert anti⁃inflammatory and brain protective effects.