血脑屏障渗透性改变的细胞和分子机制研究进展

Research progress in cellular and molecular mechanisms related to permeability alteration of blood-brain barrier

血脑屏障(BBB)稳态是维持中枢神经系统正常生理功能的基础。在阿尔茨海默病、帕金森病、多发性硬化病、脊髓侧索硬化病、癫痫、卒中和神经胶质瘤等多种神经疾病的发生、发展及转归过程中均能观察到BBB结构和功能的改变。BBB中的紧密连接和黏附连接限制了内外源性化合物的转运,使药物投递至中枢神经系统极其困难。本文综述了脑血管内皮细胞、星形胶质细胞、小胶质细胞、周细胞和基膜的形态和功能改变,连接蛋白和转运体的结构和表达异常,以及RNA干扰、模拟肽、纳米材料和高频聚焦超声等新技术对BBB渗透性影响的研究进展。

Stable permeability of blood-brain barrier（BBB） is essential to maintaining the function of the central nervous system（CNS）. The structure and permeability of BBB are changed during the development and progression of various neurological diseases such as Alzheimer disease and Parkinson disease, multiple sclerosis, lateral sclerosis, epilepsy, stroke and gliomas. Tight junctions and adherens junctions of BBB strictly limit the transportation of endogenous and exogenous compounds, making difficult the delivery of therapeutic drugs to CNS. The morphological and functional changes of the brain microvascular endothelial cells, astrocytes, microglial cells, pericytes and basement membrane, as well as the abnormal structure and expression of junctional proteins and transporters, affect the permeability alteration of BBB. New biotechnologies such as RNA interference, mimic peptides, nano materials and high-frequency focused ultrasound have been applied to study this phenomenon and explore its mechanism. This article summarizes the research progress in the permeability alteration of BBB.