中药化学成分对UGT1A1表达调控及活性的作用的研究进展.docVIP

中药化学成分对UGT1A1表达调控及活性的作用的研究进展 　　[摘要]尿苷二磷酸葡萄糖醛酸转移酶1A1（UGT1A1）是一种重要的Ⅱ相代谢酶，不仅介导了大量临床药物、非药外源物的代谢清除，同时还在维系机体内源性物质代谢平衡中发挥着至关重要的作用。UGT1A1表达/功能的改变不仅会引起药物/中药-药物相互作用，还可导致内源性物质的代谢紊乱，引发高胆红素血症、胆红素脑病及肝损伤等毒副作用。目前已发现多种临床药物及中药成分等外源物可调控UGT1A1的活性。该文结合国内外在药物代谢及毒理学相关领域新近研究进展，综述了不同类型中药化学成分（如黄酮类、香豆素类、生物碱类等）对UGT1A1表达调控及活性作用，包括中药化学成分对UGT1A1酶活性的抑制作用和中药化学成分对UGT1A1酶的诱导作用。该文能够为UGT1A1介导的中药-药物相互作用提供深入的理解和一定的参考，有助于未来指导临床上中药制剂的合理使用。 　　[关键词]尿苷二磷酸葡萄糖醛酸转移酶1A1（UGT1A1）； 中药成分； 抑制； 诱导 　　[Abstract]Uridine 5′-diphosphate-glucuronosyltransferase1A1（UGT1A1） is a major phase Ⅱ metabolism enzyme， responsible for glucuronidation and elimination of drugs and endogenous compounds， playing a vital role in sustaining endogenous metabolism balance. Therefore， changes in UGT1A1 expression/functional can not only cause adverse clinical drug/herbs-drug interactions， but also lead to metabolic disorder of endogenous substances， causing high blood bilirubin， bilirubin encephalopathy and liver injury， as well as other side effects. To date， many studies have found that a variety of clinical medicines and medicinal ingredients can regulate UGT1A1 activity. This article would summarize the advances in research on drug metabolism and toxicology in domestic and foreign literature， and investigate the regulatory effects of different types of traditional Chinese medicine（TCM） ingredients（such as flavonoids， coumarins， alkaloids） on UGT1A1 expression and activity， including inhibitory effect of TCM chemical ingredients on UGT1A1 and effect of TCM chemical ingredients on UGT1A1. It is hoped that this review could provide depth understanding and certain reference for the interaction between chemical ingredients of TCM and UGT1A1， which is of great significance to guide the rational clinical use in future. 　　[Key words]UGT1A1； chemical ingredients of traditional Chinese medicine； inhibition； induction 　　尿苷二磷酸葡萄糖醛酸?D移酶（UDP-glucuronosyltransferases，UGTs）可将许多内源性物质及外源性致癌物、药物、微量元素等转化成葡萄糖醛酸化代谢产物，随胆汁和尿液排出体外[1]。基于氨基酸序列的同源性和基因结构的相似性，人体U