摘要
目的探讨高迁移率族蛋白-1(HMGB1)在脓毒性脑病发病机制中的作用。方法将成年雄性C57BL/6J小鼠随机分为4组:假手术(Sham)组(溶剂预处理1 d,假手术)、Sham+炎性色素(ICM)组(炎性色素10 mg/kg预处理1天,假手术)、盲肠结扎穿孔(CLP)组(溶剂预处理1天,CLP建模)和CLP+ICM组(炎性色素10 mg/kg预处理1天,CLP建模)。采用Morris水迷宫评估小鼠空间记忆功能,旷场实验评估自主活动能力。术后第1天,通过血脑屏障渗漏实验评估血脑屏障完整性;Western blot检测大脑皮质紧密连接蛋白(ZO-1、Occludin和Claudin-5)以及Toll样受体4(TLR4)、内皮一氧化氮合酶(eNOS)的表达水平。结果与CLP组相比,CLP+ICM组水迷宫定位航行实验潜伏期缩短,空间探索实验目标象限停留时间和平台穿越次数增加。术后第1天血脑屏障渗透率降低;大脑皮质ZO-1、Occludin、Claudin-5表达上调;TLR4、eNOS表达水平下调。结论HMGB1可能通过激活TLR4/eNOS通路介导脓毒症小鼠血脑屏障损伤,进而促进脓毒性脑病的发生。
Objective To investigate the role of high mobility group box-1(HMGB1)in the pathogenesis of sepsis-associated encephalopathy(SAE).Methods Adult male C57BL/6J mice were randomly divided into 4 groups:Sham(vehicle pretreatment for 1 day,sham operation),Sham+ICM(Inflachromene 10 mg/kg pretreatment for 1 day,sham operation),cecal ligation and puncture(CLP)(vehicle pretreatment for 1 day,cecal ligation and puncture CLP modeling),and CLP+ICM(Inflachromene 10 mg/kg pretreatment for 1 day,CLP modeling).Morris water maze was used to evaluate spatial memory function,and open field test was used to assess spontaneous activity.On the first day after surgery,blood-brain barrier permeability was evaluated through leakage experiments.Western blot was used to detect the expression levels of tight junction proteins(ZO-1,Occludin,and Claudin-5)in the cerebral cortex,as well as Toll-like receptor 4(TLR4)and endothelial nitric oxide synthase(eNOS).Results Compared with the CLP group,the CLP+ICM group exhibited shortened latency in the water maze positioning navigation experiment,increased target quadrant dwelling time,and increased platform crossing times in the spatial probe test.On the first day after surgery,blood-brain barrier permeability was reduced;the expression of ZO-1,Occludin,and Claudin-5 in the cerebral cortex was upregulated;and the expression levels of TLR4 and eNOS were downregulated.Conclusion HMGB1 may mediate blood-brain barrier damage in septic mice by activating the TLR4/eNOS pathway,thereby promoting the occurrence of SAE.
作者
沈冬青
廖心成
伍晓妍
姚玉笙
SHEN Dongqing;LIAO Xincheng;WU Xiaoyan;YAO Yusheng(Department of Anesthesiology,Shengli Clinical Medical College of Fujian Medical University,Fuzhou,Fujian 350001,China)
出处
《福建医药杂志》
CAS
2024年第6期67-71,F0003,共6页
Fujian Medical Journal
基金
福建省卫生计生中青年骨干人才培养项目(2016-ZQN-7)
福建省卫生健康科技计划项目(2022CXA007)。
关键词
认知功能障碍
高迁移率族蛋白-1
血脑屏障
脓毒症脑病
cognitive dysfunction
high mobility group box-1 protein
blood-brain barrier
sepsis-associated encephalopa-thy
