Bohan Alan, Boyer James L
Liver Center, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Semin Liver Dis. 2002;22(2):123-36. doi: 10.1055/s-2002-30099.
Hepatocellular and canalicular transport proteins are major determinants of the hepatic uptake and biliary excretion of xenobiotics and their metabolites. Recent advances in molecular cloning have resulted in the characterization of many of these transport systems. These advances have enabled the identification of a number of drugs that are substrates for the transporters, and it has facilitated studies of mechanisms of drug-induced cholestasis. This review summarizes the normal function of hepatobiliary transporters and their alteration by drugs or other foreign compounds. Although most of these investigations have been performed in animal models of drug-induced cholestasis, the application to human forms of drug-induced cholestasis is also discussed when possible. One important finding is that genetic polymorphisms can result in changes in drug transporter expression and function that could increase susceptibility to cholestatic drug reactions.
肝细胞和胆小管转运蛋白是外源性物质及其代谢产物肝脏摄取和胆汁排泄的主要决定因素。分子克隆技术的最新进展已对许多此类转运系统进行了表征。这些进展使得能够鉴定出许多作为转运体底物的药物，并促进了对药物性胆汁淤积机制的研究。本综述总结了肝胆转运蛋白的正常功能及其被药物或其他外来化合物改变的情况。尽管这些研究大多是在药物性胆汁淤积的动物模型中进行的，但也尽可能讨论了其在人类药物性胆汁淤积中的应用。一个重要发现是，基因多态性可导致药物转运体表达和功能的改变，从而增加对胆汁淤积性药物反应的易感性。
