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血脑屏障动物模型的研究进展
王晓航1,2,陈洋1,2,戚中田1,朱勇喆1*
0
(1. 海军军医大学(第二军医大学)海军医学系生物医学防护教研室, 上海 200433;
2. 海军军医大学(第二军医大学)基础医学院, 上海 200433
*通信作者)
摘要:
血脑屏障(BBB)是中枢神经血管单元的重要结构,通过紧密连接及转运蛋白阻止神经毒性物质与病原体入侵,维护中枢神经系统内环境稳定。相较于体外模型,理想的动物模型可更好地模拟BBB生理机制,在血流动力学、屏障完整性、信号转导和物质交换等研究中起重要作用。在BBB动物模型评价方法的研究中,减少创伤、动态评估成为评价方法的重要需求; BBB动物模型的构建由经典模型动物(果蝇、非人灵长类动物)转变为转基因、人源化动物(斑马鱼、小鼠),说明在新技术发展下,与人类蛋白表达相近、适合高通量筛选的BBB动物模型是该领域的主流发展趋势。
关键词:  血脑屏障  动物模型  评价方法  转基因动物模型  人源化动物模型
DOI:10.16781/j.CN31-2187/R.20210759
投稿时间:2021-08-03修订日期:2022-03-02
基金项目:国家自然科学基金(31770181,31770187),海军军医大学(第二军医大学)创新能力培养计划(FH2019060).
Animal models of blood-brain barrier:research progress
WANG Xiao-hang1,2,CHEN Yang1,2,QI Zhong-tian1,ZHU Yong-zhe1*
(1. Department of Biomedical Defense, Faculty of Naval Medicine, Naval Medical University (Second Military Medical University), Shanghai 200433, China;
2. College of Basic Medical Sciences, Naval Medical University (Second Military Medical University), Shanghai 200433, China
*Corresponding author)
Abstract:
Blood-brain barrier (BBB) is an important structure of the neurovascular unit, and it can prevent the invasion of neurotoxic substances and pathogens through tight junctions and transporting proteins, maintaining the stability of the environment in the central nervous system. Compared with the BBB models in vitro, the ideal animal models can better simulate the physiological mechanism of BBB and play an important role in studying hemodynamics, barrier integrity, signal transduction, material exchange and so on. Reducing trauma and dynamic evaluation have become important needs in evaluating BBB models. The BBB model animals have changed from classical model animals (fruit flies and non-human primates) to transgenic and humanized animals (zebrafish and mice). With the development of new technology, BBB animal models with humanized protein expression and high-throughput screening are becoming the mainstream trend in this field.
Key words:  blood-brain barrier  animal models  evaluation method  transgenic animal model  humanized animal model