[1]沈冬青,廖心成,伍晓妍,等.高迁移率族蛋白-1通过TLR4/eNOS信号通路介导脓毒症小鼠血脑屏障损伤[J].福建医药杂志,2024,46(06):67-71.[doi:10.20148/j.fmj.2024.06.021]
　SHEN Dongqing,LIAO Xincheng,WU Xiaoyan,et al.HMGB1 mediates blood-brain barrier disruption in septic mice via TLR4/eNOS signaling pathway[J].FUJIAN MEDICAL JOURNAL,2024,46(06):67-71.[doi:10.20148/j.fmj.2024.06.021]
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高迁移率族蛋白-1通过TLR4/eNOS信号通路介导脓毒症小鼠血脑屏障损伤()
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《福建医药杂志》[ISSN:1002-2600/CN:35-1071/R]

卷:
46
期数:
2024年06期
页码:
67-71
栏目:
基础研究
出版日期:
2024-11-15

文章信息/Info

Title:
HMGB1 mediates blood-brain barrier disruption in septic mice via TLR4/eNOS signaling pathway
文章编号:
1002-2600(2024)06-0067-05
作者:
沈冬青; 廖心成; 伍晓妍; 姚玉笙
福建医科大学省立临床医学院, 福州 350001
Author(s):
SHEN Dongqing;  LIAO Xincheng;  WU Xiaoyan;  YAO Yusheng
Department of Anesthesiology, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian 350001, China
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
Keywords:
cognitive dysfunction;  high mobility group box-1 protein;  blood-brain barrier;  sepsis-associated encephalopathy
分类号:
R3
DOI:
10.20148/j.fmj.2024.06.021
文献标志码:
A
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。
Abstract:
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.

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备注/Memo

备注/Memo:
基金项目: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)
通信作者:姚玉笙,Email:fjslyys@126.com
更新日期/Last Update: 2024-11-15