缺氧条件下 miRNA：转录调控药物代谢酶和转运体的中心——十年综述。

A Decade's Review of miRNA: A Center of Transcriptional Regulation of Drugmetabolizing Enzymes and Transporters under Hypoxia.

机构信息

Research Center for High Altitude Medicine, Qinghai University, Xining, China.

Medical College, Qinghai University, Xining, China.

出版信息

Curr Drug Metab. 2021;22(9):709-725. doi: 10.2174/1389200222666210514011313.

DOI:10.2174/1389200222666210514011313

PMID:33992050

Abstract

BACKGROUND

Hypoxia has a negative effect on the cardiovascular system, nervous system, and metabolism, which contributes to potential changes in drug absorption, distribution, metabolism, and excretion (ADME). However, hypoxia can also alter the expression of microRNA (miRNA), thereby regulating drug-metabolizing enzymes, transporters, and ADME genes, such as hypoxia-inducible factor, inflammatory cytokine, nuclear receptor, etc. Therefore, it is crucial to study the role of miRNA in the regulation of drug-metabolizing enzymes and transporters under hypoxia.

METHODS

A systematic review of published studies was carried out to investigate the role of miRNA in the regulation of drug-metabolizing enzymes and transporters under hypoxia. Data and information on expression changes in miRNA, drug-metabolizing enzymes, and transporters under hypoxia were analyzed and summarized.

RESULTS

Hypoxia can up or down-regulate the expression of miRNA. The effect of hypoxia on Cytochrome P450 (CYP450) is still a subject of debate. The widespread belief is that hypoxia decreased the activity and expression of CYP1A1, CYP1A2, CYP2E1, and CYP3A1 and increased those of CYP3A6 and CYP2D1 in rats. Hypoxia increased the expression of a multidrug resistance-associated protein, breast cancer resistance protein, peptide transporter, organic cation transporter, and organic anion transporter. miRNA negatively regulated the expression of drugmetabolizing enzymes and transporters.

CONCLUSION

The findings of this review indicated that miRNA plays a key role in the expression changes of drugmetabolizing enzymes and transporters under hypoxia.

摘要

背景

缺氧对心血管系统、神经系统和新陈代谢都有负面影响，这可能导致药物吸收、分布、代谢和排泄（ADME）发生变化。然而，缺氧也可以改变 microRNA（miRNA）的表达，从而调节药物代谢酶、转运体和 ADME 基因，如缺氧诱导因子、炎症细胞因子、核受体等。因此，研究 miRNA 在缺氧下调控药物代谢酶和转运体中的作用至关重要。

方法

对已发表的研究进行系统评价，以研究 miRNA 在缺氧下调控药物代谢酶和转运体中的作用。分析和总结了缺氧下 miRNA、药物代谢酶和转运体表达变化的数据和信息。

结果

缺氧可上调或下调 miRNA 的表达。缺氧对细胞色素 P450（CYP450）的影响仍存在争议。普遍认为，缺氧降低了大鼠 CYP1A1、CYP1A2、CYP2E1 和 CYP3A1 的活性和表达，增加了 CYP3A6 和 CYP2D1 的表达。缺氧增加了多药耐药相关蛋白、乳腺癌耐药蛋白、肽转运体、有机阳离子转运体和有机阴离子转运体的表达。miRNA 负调控药物代谢酶和转运体的表达。