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
余信远 1简志宏 1刘仁忠 1冯艳萍2
作者信息
- 1. 武汉大学人民医院神经外科 湖北 武汉 430060
- 2. 武汉大学人民医院麻醉科 湖北 武汉 430060
- 折叠
摘要
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.
Abstract
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.
关键词
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Key words
Ischemic Stroke/Therapeutic Hypothermia/Interferon Regulatory Factor 4/Macrophage Polarization/Inflammatory Response引用本文复制引用
基金项目
国家自然科学基金项目资助项目(81870939)
出版年
2024
NETL
NSTL
万方数据