摘要
血脑脊液屏障是由脑微血管内皮细胞、星形胶质细胞和周皮细胞等组成的动态生理结构,对中枢神经系统内环境稳态的维持发挥至关重要的作用。P-糖蛋白作为血脑脊液屏障上一种常见膜蛋白,它在脑微血管内皮细胞中大量表达,限制毒性物质和大量治疗中枢神经系统的药物进入脑内。因此对P-糖蛋白在血脑脊液屏障中的外排转运机制的了解是神经系统疾病治疗的一个突破点。该文主要对P-糖蛋白的基本结构、转运途径、在生理与病理情况下P-糖蛋白的调节机制以及P-糖蛋白抑制剂研究进展等进行综述,对中枢神经系统药物研发以及提高血脑脊液屏障对治疗药物通透性研究提供参考。
Blood-cerebrospinal fluid barrier（blood-CSF barrier） is a dynamic physiological structure,which is composed of brain microvascular endothelial cells, astrocytes and pericytes,playing an important role in maintaining homeostasis in the central nervous system （CNS）. P-glycoprotein （P-gp）is a common membrane protein in the blood cerebrospinal fluid barrier,which is expressed in the brain microvascular endothelial cells, and it limits the toxic substances and a large number of drugs for the treatment of the central nervous system into the brain. Therefore the efflux transport mechanism of P-gp in the blood-CSF barrier is a break though point for the treatment of nervous system disease. This article mainly reviews research progress on the basic structure and trans-port mechanism of P-gp,it＇s regulation mechanism in the physiological and pathological conditions and inhibitors,to provide references for drug development and blood-CSF barrier transport mechanism of CNS.
出处
《神经药理学报》
2016年第2期53-64,共12页
Acta Neuropharmacologica
基金
国家自然科学基金项目(No.81274005)
河北省自然科学基金项目(No.2016208058)
关键词
P-糖蛋白
基本结构
转运机制:调节机制
抑制剂
P-glycoprotein
basic structure
transport mechanism
regulation mechanism
inhibitor
