基于血脑屏障转运体的中枢神经系统疾病治疗策略探讨与展望

Exploration and expectation on treatment strategies of central nervous system diseases based on transporters at blood-brain barrier

血脑屏障(blood-brain barrier,BBB)结构和功能的完整是维持脑内部稳态和正常功能的必要条件。BBB的特殊结构使大分子和亲水性物质必需由BBB上的物质转运体介导进入脑内。同时,BBB上的外排转运体还能将一些内、外源性物质排出脑内。本文介绍了一些与中枢神经系统(central nervous system,CNS)药物密切相关的一些BBB转运体,诸如ABC转运体、葡萄糖转运体、转铁蛋白受体、胰岛素受体等,综述内容包括它们的功能、分布、与CNS疾病的关系、与CNS药物的关系以及影响它们表达的因素等。阐明这些要素对促进CNS药物经BBB转运入脑具有重要意义,此外,也为探究某些CNS疾病发病机制及其治疗提供新思路。

The structural and functional integrity of the blood-brain barrier(BBB)is a prerequisite for the maintenance of the brain homeostasis and function.Because of the structural peculiarities of the BBB,macromolecules and hydrophilic substances can pass through it only by some BBB transporter-mediated mechanisms.At the same time,the BBB is also responsible for deportation of some endogenous or exogenous substances from the brain through the efflux transporters.The current research advances on some important transporters at the BBB closely related to central nervous system(CNS)drugs,have been summarized in this review.These transporters include ABC transporters,glucose transporters,transferring receptor,insulin receptor and so on.This review offers a overview of structures,functions,distributions,relationships with CNS disease and drugs and the factors influencing their expression of some transporters at the BBB.Clarifying these elements could make a big difference to promote the CNS drugs to reach the brain across the BBB.Moreover,it provides new insights for exploring pathogenic mechanisms of some CNS diseases and their treatment.