吉马酮调节HMGB1-RAGE信号通路对缺血性脑卒中大鼠神经炎症的影响  

Effect of germarone modulating HMGB1-RAGE signaling pathway on neuroinflammation in ischemic stroke rats

作　　者：刘凡诗 陈浩 LIU Fanshi;CHEN Hao(College of Clinical Medicine and Technology,Sichuan Health Rehabilitation Vocational College,Zigong 643000,Sichuan,China;Zigong City Ecological Environment Bureau,Zigong 643000,Sichuan,China)

机构地区：[1]四川卫生康复职业学院临床医技学院,自贡643000 [2]自贡市生态环境局,自贡643000

出　　处：《医学研究与战创伤救治》2025年第2期127-134,共8页Journal of Medical Research & Combat Trauma Care

基　　金：四川省医学科研课题(S20032)。

摘　　要：目的 旨在探讨吉马酮(GM)对缺血性脑卒中大鼠神经炎症的影响,并基于高迁移率基团盒1(HMGB1)/晚期糖基化终产物(RAGE)/核因子-κB(NF-κB)信号通路介导的小胶质细胞活化探讨其潜在的作用机制。方法 采用短暂性大脑中动脉闭塞(MCAO)法构建缺血性脑卒中大鼠模型。将MCAO大鼠随机分为4组,每组24只:MCAO组、吉马酮治疗组(GM组;腹腔注射GM 20mg/kg)、重组HMGB1处理组(rHMGB1组;腹腔注射重组HMGB1 8μg/kg)和重组HMGB1+吉马酮处理组(rHMGB1+GM组;腹腔注射重组HMGB1 8μg/kg+GM 20 mg/kg)。Sham组(n=24)大鼠仅麻醉后暴露颈动脉,不进行MCA闭塞。采用改良神经功能缺损评分、TTC染色、苏木精伊红染色、Nissl染色、TUNEL测定评估大鼠的神经功能、脑梗死体积、脑组织病理损伤和神经元死亡。采用免疫荧光与ELISA分析小胶质细胞M1/M2极化。蛋白免疫印迹分析用于检测相关蛋白表达情况。结果 相较于MCAO组,GM处理能够降低MCAO大鼠的神经功能缺损评分和脑梗死体积,减轻脑水肿、脑组织病理损伤、神经元死亡和神经炎症反应,抑制小胶质细胞M1极化并促进M2极化,抑制NF-κB活化和HMGB1、RAGE蛋白表达(P<0.05)。重组HMGB1处理能够在一定程度上逆转GM对MCAO大鼠的神经保护作用(P<0.05)。结论 GM通过调节HMGB1/RAGE/NF-κB轴来抑制小胶质细胞M1极化并促进M2极化,从而减轻神经炎症反应,在缺血性脑卒中发挥神经保护作用。Objective To investigate the effects of germarone(GM)on neuroinflammation in ischemic stroke rats,and to explore the potential mechanism of microglia activation mediated by high mobility group box 1(HMGB1)/receptor for advanced glycosylation end product(RAGE)/nuclear factorκB(NF-κB)signaling pathway.Methods TTransient middle cerebral artery occlusion(MCAO)was used to establish a rat model of ischemic stroke.MCAO rats were randomly divided into 4 groups with 24 rats in each group:MCAO group,gemalone treatment group(GM group;Intraperitoneal injection of GM 20mg/kg and recombinant HMGB1 treatment group(rHMGB1 group;Intraperitoneal injection of recombinant HMGB18μg/kg and recombinant HMGB1+gemalone treatment group(rHMGB1+GM group;Intraperitoneally injected recombinant HMGB18μg/kg+GM 20mg/kg).In Sham group(n=24),only carotid artery was exposed after anesthesia,and MCA occlusion was not performed.Neural function,infarct volume,pathological injury of brain tissue and neuronal death were evaluated by modified neural function deficit score,TTC staining,hematoxylin eosin staining,Nissl staining and TUNEL assay.The M1/M2 polarization of microglia was analyzed by immunofluorescence and ELISA.Western blot analysis was used to detect the expression of related proteins.Results TCompared with the MCAO group,GM treatment was able to reduce the neurological deficit score and cerebral infarction volume, alleviate cerebral edema, cerebral histopathological injury, neu-ronal death and neuroinflammatory response, inhibit microglia M1 polarization and promote M2 polarization, and inhibit NF-κB activa-tion and the expression of HMGB1 and RAGE proteins in MCAO rats (P<0. 05). Recombinant HMGB1 treatment was able to reverse the neuroprotective effect of GM on MCAO rats to some extent (P<0. 05). Conclusion TGM can inhibit microglia M1 polarization and promote M2 polarization by regulating HMGB1/ RAGE/ NF-κB axis, thereby reducing neuroinflammatory response and playing a neuroprotective role in ischemic stroke.

关 键 词：缺血性脑卒中 神经炎症 吉马酮 小胶质细胞 高迁移率基团盒1 

分 类 号：R743[医药卫生—神经病学与精神病学]