缺氧对多药耐药相关蛋白2表达及调控机制的影响

发布时间：2018-08-28 19:39

【摘要】：药物外排转运蛋白对药代动力学参数变化起着关键性作用。近年来研究较多的外排型转运蛋白除了P-糖蛋白(P-glycoprotein,P-gp)、乳腺癌耐药蛋白(breast cancer resistance protein,BCRP)外,多药耐药相关蛋白2(multidrug resistance protein 2,MRP2)逐渐成为了研究的热点。肿瘤微缺氧环境中一些信号转导通路、转录因子参与MRP2基因的表达调控,这些因子包括过氧化物酶体增殖剂激活受体(peroxisome proliferators-activated receptors,PPARα)、核因子-κB(nuclear factorκB,NF-κB)、孕烷X受体(pregnane X receptor,PXR)、法尼醇X受体(farnesoid X receptor,FXR)、组成型雄烷受体(constitutive androstane receptor,CAR)和micro RNA等,但MRP2在缺氧条件下的调控机制尚不完全清楚,且是一个很复杂的过程。MRP2作为最主要的外排转运蛋白之一,多种常用药物及抑制剂是其底物,MRP2的表达变化会显著影响这些底物药代动力学(吸收、分布、代谢、排泄)。同时,缺氧状态下MRP2不仅是由单一的信号通路或者某个转录基因调控,而是涉及多个信号通路以及诸多基因,从而构成一个调控网络。
[Abstract]:Drug efflux transporter plays a key role in the change of pharmacokinetic parameters. In recent years, in addition to P-glycoprotein (P-gp) and breast cancer resistance protein (breast cancer resistance protein,BCRP), multidrug resistance-associated protein (2 (multidrug resistance protein 2 / MRP2) has become a hot research topic. Some signal transduction pathways in tumor microanoxia environment, transcription factors involved in the regulation of MRP2 gene expression, These factors include peroxisome proliferator activated receptor (peroxisome proliferators-activated receptors,PPAR 伪), nuclear factor- 魏 B (nuclear factor 魏 B, NF- 魏 B), pregnancy X receptor (pregnane X receptor,PXR, farnesol X receptor (farnesoid X receptor,FXR), constitutive androgen receptor (constitutive androstane receptor,CAR) and micro RNA, etc. However, the regulatory mechanism of MRP2 under hypoxia is not fully understood, and it is a very complex process. MRP2 is one of the most important efflux transporters. The changes of MRP2 expression in a variety of commonly used drugs and inhibitors may significantly affect the pharmacokinetics (absorption, distribution, metabolism, excretion) of these substrates. At the same time, under anoxic condition, MRP2 is not only regulated by a single signal pathway or a transcriptional gene, but also involves multiple signaling pathways and many genes, thus forming a regulatory network.
【作者单位】：兰州大学药学院;兰州军区兰州总医院全军高原损伤防治重点实验室;甘肃省妇幼保健院药剂科;
【基金】：国家科技重大专项(2008ZXJ09014-010) 国家自然科学基金(81401552,81403004,81673508) 全军后勤科研“十二五”重大项目(AWS14L0005) 全军医学科研"十二五"重点项目(BWS12J012) 甘肃省自然科学基金(145RJZA111)~~
【分类号】：R96

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