低氧对药物代谢酶和转运体的影响及其调控机制
敏琼^1,2, 封士兰¹, 鹿辉², 李文斌², 王昌², 张娟红², 王荣^1,2,*
1兰州大学药学院，兰州 730000；²兰州军区兰州总医院全军高原环境损伤防治重点实验室，兰州 730050
摘要
低氧环境中药物在体内的代谢会受到显著影响，其中药物代谢动力学参数、药物代谢酶及转运体的表达及功能均会发生变化。研究表明机体在低氧状态下会释放一系列炎性因子对药物代谢产生调控。此外，低氧诱导因子1α (hypoxia inducible factor 1α, HIF-1α)和微小RNA (microRNA, miRNA)介导的通路均对药物代谢有调控作用。本文对低氧状态下药物代谢的变化情况及其单因素调控机制进行综述，并提出多因素调控机制的推测及展望。
关键词： 低氧; 药物代谢酶; 转运体; 调控机制
分类号：R966

Modulation of drug-metabolizing enzymes and transporters under hypoxia environment
MIN Qiong^1,2, FENG Shi-Lan¹, LU Hui², LI Wen-Bin², WANG Chang², ZHANG Juan-Hong², WANG Rong^1,2,*
1College of Pharmacy, Lanzhou University, Lanzhou 730000, China；²Key Laboratory of the Plateau Environmental Damage Control, Lanzhou General Hospital of Lanzhou Military Command, PLA, Lanzhou 730050, China
Abstract
Drug metabolism is significantly affected under hypoxia environment with changes of pharmacokinetics, expression and function of drug-metabolizing enzymes and transporters. Studies have shown that hypoxia increases the release of a series of inflammatory cytokines which can modulate drug metabolism. Besides, both hypoxia inducible factor 1α (HIF-1α) and microRNA-mediated pathways play a role in regulating drug metabolism. This article reviewed the impact and single-factor modulating mechanisms of drug metabolism under hypoxia, and put forward the speculation and prospects of multi-factor modulating mechanisms.


Key words: Hypoxia; drug-metabolizing enzymes; transporters; modulating mechanism

收稿日期：2018-04-19　　录用日期：2018-08-10
通讯作者：王荣　　E-mail: wangrong-69@163.com
DOI: 10.13294/j.aps.2018.0082
引用本文：
敏琼, 封士兰, 鹿辉, 李文斌, 王昌, 张娟红, 王荣. 低氧对药物代谢酶和转运体的影响及其调控机制[J]. 生理学报 2019; 71 (2): 336-342.
MIN Qiong, FENG Shi-Lan, LU Hui, LI Wen-Bin, WANG Chang, ZHANG Juan-Hong, WANG Rong. Modulation of drug-metabolizing enzymes and transporters under hypoxia environment. Acta Physiol Sin 2019; 71 (2): 336-342 (in Chinese with English abstract).



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