高原低氧对药物跨血脑屏障转运的调节作用及机制  

The modulation and mechanisms of high-altitude hypoxia in drug transport across the blood-brain barrier

作　　者：刘贵琴 白雪 杨建鑫 段雅彬 朱俊博 田露 李向阳[1,4] LIU Gui-qin;BAI Xue;YANG Jian-xin;DUAN Ya-bin;ZHU Jun-bo;TIAN Lu;LI Xiang-yang(Research Center for High Altitude Medicine,Qinghai University,Xining 810001,China;Affiliated Hospital of Qinghai University,Xining 810001,China;Medical College of Qinghai University,Xining 810001,China;State Key Laboratory of Plateau Ecology and Agriculture,Qinghai University,Xining 810016,China)

机构地区：[1]青海大学高原医学研究中心,青海西宁810001 [2]青海大学附属医院,青海西宁810001 [3]青海大学医学院,青海西宁810001 [4]青海大学三江源生态与高原农牧业国家重点实验室,青海西宁810016

出　　处：《药学学报》2023年第3期659-671,共13页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(82260731);青海省创新平台建设专项(2021-ZJ-T03)。

摘　　要：高原低氧环境下机体中枢神经系统功能发生显著改变,这些变化引发中枢神经系统疾病,影响药物体内代谢过程。血脑屏障是维持中枢神经系统稳定的必要条件,在药物代谢调节中发挥关键作用,屏障结构和功能变化影响药物脑部转运。高原低氧环境下血脑屏障结构和功能及药物跨血脑屏障转运变化,是受脑微血管内皮细胞、星形胶质细胞和周细胞等细胞调节,或是受药物转运体和药物代谢酶等药物代谢因素调节。本文通过综述高原低氧环境对血脑屏障结构和功能的影响及血脑屏障变化对药物代谢的影响,探讨高原低氧环境中血脑屏障与转录因子、炎症因子和核受体等相关通路对药物转运的调节作用及潜在机制。The function of the central nervous system was significantly altered under high-altitude hypoxia,and these changes lead to central nervous system disease and affected the metabolism of drugs in vivo.The bloodbrain barrier is essential for maintaining central nervous system stability and plays a key role in the regulation of drug metabolism,and barrier structure and dysfunction affect drug transport to the brain.Changes in the structure and function of the blood-brain barrier and the transport of drugs across the blood-brain barrier under high-altitude hypoxia are regulated by changes in brain microvascular endothelial cells,astrocytes and pericytes,and are regulated by drug metabolism factors such as drug transporters and drug metabolizing enzymes.This article reviews the effects of high-altitude hypoxia on the structure and function of the blood-brain barrier and the effects of changes in the blood-brain barrier on drug metabolism.We investigate the regulatory effects and underlying mechanisms of the blood-brain barrier and related pathways such as transcription factors,inflammatory factors and nuclear receptors on drug transport under high-altitude hypoxia.

关 键 词：血脑屏障 高原低氧 药物转运体 药物代谢酶 药物转运 

分 类 号：R917[医药卫生—药物分析学]