【摘要】 尿苷二磷酸葡萄糖醛酸转移酶(UDP-glucuro-nosyltransferase,UGT)属于Ⅱ相药物代谢酶。它能催化葡醛酸与其相应底物结合,是化学物质在生物体内进行Ⅱ相生物转化时最重要的一类酶。越来越多的研究发现,孕烷X受体(pregnaneXreceptor,PXR)、组成型雄甾烷受体(constitutiveandrostanere-ceptor,CAR)等孤儿核受体(orphannuclearreceptors)及其他转录因子能调节UGT基因的转录,这些受体及因子分布和活性的差异可导致UGT酶表达和分布的差异。此外,研究表明化合物通过核受体(NR)介导的UGT酶表达量的变化可能是影响化合物体内代谢的一条重要途径。由于UGT酶表达量与激素平衡、药物疗效、药物毒副作用及肿瘤等多种疾病发病预后密切相关,所以研究核受体对Ⅱ相代谢酶的调节作用在预测药物相互作用、指导临床合理用药及人类疾病的预防等方面都具有重要意义。更多还原

【Abstract】 UDP-glucuronosyltransferases(UGTs) belong to the Phase II drug metabolizing enzymes.UGTs mediate transformations of glucuronic acid to xeno-and endobiotic chemicals,and it is the most important type of enzymes which involved in biotransformation of phaseⅡ.More and more evidences have demonstrated that orphan nuclear receptors,such as pregnane X receptor(PXR),constitutive androstane receptor(CAR) and other transcriptional factors can regulate UGTs,differences of the factors above in distribution and activity can induce diversity of expression and activity of UGTs.Besides,researches indicated that the NR-mediated regulations of UGTs may contribute to variations of internal metabolism of compounds.In light of the expression of UGTs correlated to hormone homeostasis,therapeutic and side effects of medicine,incidence and prognosis of tumors and other diseases closely,therefore,elucidating UGT regulation by nuclear receptors has broad significance in drug interactions prediction and rational administration,human disease prevention and so on.更多还原