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羧酸酯酶(carboxylesterase,CES)是一类重要的Ⅰ相药物代谢酶,参与许多临床抗癌药物、氨基甲酸酯、拟除虫菊酯类杀虫剂、环境中有毒物质以及前致癌物的体内代谢。有研究表明,许多核受体(nuclear receptor,NR)家族成员在调控人和动物肝脏及肠道CES的表达和活性方面发挥着重要作用。本文查阅有关文献,综述NR对人和动物CES调节作用的研究进展,评价其在药物代谢、药物相互作用等方面的意义。近年来,随着基因敲除小鼠模型和转基因小鼠模型的应用,孕甾烷X受体蛋白(pregnane X receptor,PXR,NR1I2)和雄甾烷X受体蛋白(constitutive androstane receptor,CAR,NR1I3)调控CES的转录机制逐步被阐明,其他NR对CES调控机制的研究也有所突破,但目前有关NR对CES调节方面的研究大多局限于啮齿动物模型,后续可通过运用人源化小鼠模型以及临床试验等来深入探讨NR调控CES的作用机制以指导新药开发及临床合理用药。
Carboxylesterase (CES) is an important phase I drug metabolizing enzyme involved in many clinical anti-cancer drugs, carbamates, pyrethroid insecticides, toxicants in the environment and pro-carcinogens metabolism. Studies have shown that many members of the nuclear receptor (NR) family play an important role in regulating the expression and activity of CES in the liver and intestine of humans and animals. In this paper, we review the literature, review the research progress of NR on the regulation of human and animal CES, and evaluate its significance in drug metabolism and drug interactions. In recent years, pregnane X receptor (PXR, NR1I2) and the constitutive androstane receptor (CAR, NR1I3) have been used in both knockout mice and transgenic mouse models. ) Has been gradually clarified in the transcriptional regulation mechanism of CES. Other NRs have also made breakthroughs in the research of CES regulatory mechanisms. However, the current research on the regulation of CES by NR is mostly confined to rodent models. The subsequent studies can be carried out by using humanized mouse models and Clinical trials to further explore the mechanism of NR regulation of CES to guide the development of new drugs and clinical rational use of drugs.