脂多糖破坏血脑屏障与脓毒症相关脑病发生的研究进展

Research advances in the mechanism of blood-brain barrier disruption by lipopolysaccharide and the onset of sepsis-associated encephalopathy

作为中枢神经系统(central nervous system,CNS)与外周环境交界处的屏障结构,血脑屏障(bloodbrain barrier,BBB)成功地将脑组织中的循环血液与CNS分离,同时严格控制循环血液与脑组织之间的物质交换,如营养物质的运输和代谢废物的排出,从而维持CNS的稳态环境。脂多糖(lipopolysaccharide,LPS)是革兰氏阴性菌的细胞壁成分,可损害BBB的屏障功能并进一步促进脓毒症相关脑病(sepsis-associated encephalopathy,SAE)的发生和发展。在这里,我们对LPS通过中心环节和其他间接环节损伤BBB的机制以及这些过程与SAE之间的关系进行了文献综述。我们认为当LPS对BBB造成损伤之后,大量的免疫细胞与炎症因子进入脑组织中并且激活脑部的免疫细胞,甚至组成BBB的神经血管单元也会受到影响并介导部分神经炎症和氧化应激等反应,并进一步损伤BBB。这样的恶性循环最终导致SAE的发生。因此,我们最后提出可以尝试通过靶向阻断LPS破坏BBB的屏障功能来预防和治疗SAE。

As a barrier structure at the junction of the central nervous system(CNS)and the peripheral environment,the blood-brain barrier(BBB)successfully separates the circulating blood in brain tissue from the CNS and strictly controls material exchange between circulating blood and brain tissue,such as the transport of nutrients and the expulsion of metabolic wastes,thereby maintaining the homeostasis of the CNS.Lipopolysaccharide(LPS)is a component of the cell wall of Gram-negative bacteria and can impair the barrier function of the BBB and further promote the development and progression of sepsis-associated encephalopathy(SAE).This article reviews the mechanisms by which LPS injures the BBB via central links and other indirect links,as well as the association between these processes and SAE.We believe that when LPS causes damage to the BBB,a large number of immune cells and inflammatory factors enter brain tissue and activate immune cells of the brain,and even the neurovascular units that make up the BBB are affected and mediate the responses such as partial neuroinflammatory response and oxidative stress response,which causes further damage to the BBB.Such a vicious cycle eventually leads to the development of SAE,and therefore,we finally propose that targeted blockade of the disruption of BBB barrier function by LPS can be used for the prevention and treatment of SAE.