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血脑屏障上的转运蛋白及中药有效成分跨血脑屏障转运研究进展

陈阳1，朱臻宇1，洪战英1，柴逸峰2*

[1.第二军医大学药学院药物分析学教研室，上海市药物(中药)代谢产物研究重点实验室，上海 200433;2.第二军医大学药学院，上海 200433]

[摘要]本文介绍了血脑屏障的结构、功能及该部位的转运蛋白(ATP结合盒转运蛋白和溶质载体转运蛋白)，以及它们在血脑屏障转运过程中的作用。通过脑微血管内皮细胞模型和在体脑微透析技术，定性定量地探讨了转运蛋白在中药有效成分跨血脑屏障中的作用。

[关键词]血脑屏障；ATP结合盒；溶质载体；转运蛋白；中药

[中图分类号]R285[文献标志码]A

DOI：10.5428/pcar20150201

基金项目国家自然科学基金(81173020，81373376)

作者简介陈阳(男)，硕士生.

[收稿日期]2014-09-11

Research progress of transporter proteins and the transport process of active components of Chinese materia medica across the blood brain barrier

CHEN Yang1，ZHU ZhenYu1，HONG ZhanYing1，CHAI YiFeng2*[1.Department of Pharmaceutical Analysis，School of Pharmacy, Second Military Medical University，Shanghai Key Laboratory for Pharmaceutical (Chinese Materia Medica) Metabolites Research，Shanghai 200433，China;2.School of Pharmacy, Second Military Medical University，Shanghai 200433，China]

ABSTRACT[]This article briefly presented the structure and function of the blood brain barrier(BBB) and the transporter proteins at this site，including ATP binding cassette transporter protein，solute carrier transporter proteins and their role in the transport process of BBB. And the article also summarized the qualitative and quantitative evaluations of drug transport across the BBB，mainly through the model of brain microvascular endothelial cells in vitro and brain microdialysis techniques in vivo and their application to the study of Chinese materia medica. The function of transporter proteins in the transport of active components of Chinese materia medica across the BBB was also discussed.

[KEY WORDS]blood brain barrier；ATP-binding cassette；solute carrier；transporter proteins；Chinese materia medica

[Pharm Care Res，2015，15(2)：81-87]

E-mail：cpu09452@126.com

*通信作者(Corresponding author)：柴逸峰，E-mail:yfchai@smmu.edu.cn

血脑屏障(blood brain barrier，BBB)是重要的动态屏障层，覆盖了整个中枢神经系统(central nervous systems，CNS)，主要负责保护CNS免受有潜在神经毒性的外源性物质的侵害，使大脑能够正常运转。BBB依赖特殊的血管内皮结构及转运蛋白来发挥屏障功能，这些转运蛋白负责识别和外排有害物质并吸收有利物质，其中包括ATP结合盒(ATP-binding cassette,ABC) 转运蛋白和溶质载体(solute carrier，SLC)转运体。SLC转运体又包括有机阳离子(organic cation transporter，OCT)和有机阴离子(organic anion transporter，OAT) 转运子，及转运营养物质的如葡萄糖转运子(glucose transporter，GLUT) 等[1-3]。CNS疾病如阿尔兹海默症、缺血性脑中风等已成为严重威胁人类健康的疾病。 这类疾病多为慢性病，病程长，治疗难度大，但目前药物很难有效透过BBB对这类疾病进行治疗，这在一定程度上限制了新药的开发以及对药物作用机制的研究。……