首页|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

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

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

Ischemic StrokeTherapeutic HypothermiaInterferon Regulatory Factor 4Macrophage PolarizationInflammatory Response

余信远、简志宏、刘仁忠、冯艳萍

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武汉大学人民医院神经外科 湖北 武汉 430060

武汉大学人民医院麻醉科 湖北 武汉 430060

缺血性脑卒中 治疗性亚低温 干扰素调节因子4 巨噬细胞极化 炎症反应

国家自然科学基金项目资助项目

81870939

2024

武汉大学学报(医学版)
武汉大学

武汉大学学报(医学版)

CSTPCD
影响因子:0.959
ISSN:1671-8852
年,卷(期):2024.45(6)