Center for Liver, Digestive and Metabolic Diseases, Department of Pediatrics, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
J Steroid Biochem Mol Biol. 2012 Jul;130(3-5):147-58. doi: 10.1016/j.jsbmb.2011.06.012. Epub 2011 Jul 20.
Cholestatic liver disorders encompass hepatobiliary diseases of diverse etiologies characterized by the accumulation of bile acids, bilirubin and cholesterol as the result of impaired secretion of bile. Members of the nuclear receptor (NR) family of ligand-modulated transcription factors are implicated in the adaptive response to cholestasis. NRs coordinately regulate bile acid and phospholipid transporter genes required for hepatobiliary transport, as well as the phases I and II metabolizing enzymes involved in processing of their substrates. In this review we will focus on FXR and PXR, two members of the NR family whose activities are regulated by bile acids. In addition, we also discuss the potential of pharmacological modulators of these receptors as novel therapies for cholestatic disorders.
胆汁淤积性肝病包括多种病因的肝胆疾病，其特征是胆汁分泌受损导致胆汁酸、胆红素和胆固醇的积累。核受体 (NR) 家族的配体调节转录因子成员参与了对胆汁淤积的适应性反应。NRs 协调调节胆汁酸和磷脂转运蛋白基因，这些基因是肝胆转运所必需的，同时也调节参与其底物代谢的 I 相和 II 相代谢酶。在这篇综述中，我们将重点介绍 FXR 和 PXR，这两个 NR 家族的成员，它们的活性受胆汁酸调节。此外，我们还讨论了这些受体的药理学调节剂作为胆汁淤积性疾病新疗法的潜力。
