血脑屏障在脓毒症相关性脑病中变化的研究进展
Research progress on the changes of blood-brain barrier in sepsis-associated encephalopathy
郑晓彧 1向钱 1董晓旭 1沈阳 2方巍 2杨洪娜2
作者信息
- 1. 山东大学,济南 250012;山东省立医院,山东第一医科大学附属省立医院重症医学科,济南 250000
- 2. 山东省立医院,山东第一医科大学附属省立医院重症医学科,济南 250000
- 折叠
摘要
脓毒症相关性脑病(SAE)是脓毒症最常见的并发症,在脓毒症中的发病率高达70％,也是导致脓毒症病死率和致残率增加的原因.SAE的具体发病机制仍不清楚,目前研究提示,血脑屏障(BBB)功能障碍、神经炎症、神经胶质细胞过度激活以及脑微循环障碍参与到SAE的发生发展过程中.BBB作为中枢神经系统与外周系统之间复杂的细胞结构,严格控制物质的进入和流出,在维持中枢神经系统生化和免疫环境稳态中发挥着重要作用.在发生脓毒症过程中,外周产生的炎症因子和活性氧化物质可以直接或者间接引起BBB通透性增加和结构性破坏,使这些毒性物质进入中枢神经系统引起胶质细胞(小胶质细胞、星形胶质细胞)激活、神经递质失衡、线粒体功能障碍和神经元凋亡,这些过程反过来作用于BBB,通过下调细胞间紧密连接蛋白从而增加其通透性和完整性的破坏.因此,本文重点介绍了BBB在SAE中的结构和功能变化,以及这些变化是如何导致SAE的发生发展,以寻求靶向BBB治疗SAE的方法.
Abstract
Sepsis-associated encephalopathy(SAE)is the most common neurological complication of sepsis,with an incidence of up to 70％in sepsis,and contributes to the increased mortality and disability in sepsis.To date,the exact pathogenesis of SAE is not clear.Most of current researches indicated that blood-brain barrier(BBB)dysfunction,active neuroinflammation,glial cell over activation as well as cerebral microcirculation dysfunction contributed to the pathophysiology of SAE.BBB,as a complex cellular structure between the central nervous system and the peripheral system,strictly controls the entrance and discharge of substances and plays an important role in maintaining the balance between biochemical system and immune system of central system.During the progress of sepsis,inflammatory cytokines and reactive oxygen species resulting from peripheral system directly or indirectly resulted in the damage to the integrity and structure of BBB,which helped above species easily enter into the central system.Above these damages caused glial cell activation(microglia and astrocyte),the imbalance of neurotransmitters,mitochondrial dysfunction and neural apoptosis,which also reversely contributed to the damage to the integrity and permeability of BBB via decreasing the expression of tight junctional protein between cells.Therefore,this review focuses on the structural and functional changes of BBB in SAE,and how these changes lead to the development of SAE,in order to seek a BBB-targeted therapy for SAE.
关键词
脓毒症相关性脑病/血脑屏障/内皮细胞/星形胶质细胞/紧密连接Key words
Sepsis-associated encephalopathy/Blood-brain barrier/Endothelial cell/Astrocyte/Tight junction引用本文复制引用
基金项目
山东省自然科学基金(ZR2023MH379)
山东省自然科学基金(ZR2021QH365)
出版年
2024
NETL
NSTL
万方数据