血脑屏障体外模型研究进展

脑毛细血管上的特殊结构单元为大脑提供氧气和养分,与此同时形成一种限制性屏障,称为血脑屏障(BBB),该结构单元由单层脑微血管内皮细胞构成,内皮细胞外侧的周细胞、基膜以及星形胶质细胞的足突也参与了血脑屏障的形成.血脑屏障是一种选择性渗透屏障,大多数中枢神经系统候选药物在血脑屏障中的渗透性差,用实验动物进行药物筛选具有成本高、周期长、成功率低等缺点.此外,直接在人体中试验有违道德伦理,但建立可靠的体外血脑屏障模型可以简化实验过程、缩短试验周期、实验结果更易测定,因此建立体外BBB模型可以极大地加快中枢神经系统药物的研发.目前已研究的模型主要可以分为3类:单培养、共培养、三培养,这些模型由简单到复杂,与体内血脑屏障的相似性也越来越高.本文就目前现有的血脑屏障模型进行综述,以期未来在体外BBB模型设计中有新的思路.

Advances of Blood-brain Barrier Model In Vitro

The special structural unit on the brain's capillaries supplies oxygen and nutrients to the brain, while at the same time forming a restrictive barrier called blood-brain barrier (BBB). The structural unit is mainly composed of a single layer of brain microvascular endothelial cells, surrounding by endothelial cells, as well as the neurons, microglia, and astrocytes, are involved in the formation of the blood-brain barrier. The blood-brain barrier is a selective permeation barrier, most of the central nervous system drug candidates have poor permeability in the blood-brain barrier. The disadvantages of drug screening experiments in laboratory animals are high cost, long cycle, and low accuracy. Besides, directly test in the human body is unethical. But establishing a reliable model of extracorporeal blood-brain barrier can simplify the experimental process, shorten the test period, and make the experimental results easier to determine. Therefore, the establishment of an in vitro BBB model can greatly accelerate the development of central nervous system drugs. The models that have been studied can be divided into three categories: single culture, co-culture, and triple culture. These models range from simple to complex, and more similar to blood-brain barrier in vivo. This article reviews the current blood-brain barrier model, and we expect it can provide new ideas for the design of in vitro BBB models in the future.