Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Austria.
Hepatology. 2017 Apr;65(4):1393-1404. doi: 10.1002/hep.28991. Epub 2017 Mar 7.
The identification of the key regulators of bile acid (BA) synthesis and transport within the enterohepatic circulation has revealed potential targets for pharmacological therapies of cholestatic liver diseases. Novel drug targets include the bile BA receptors, farnesoid X receptor and TGR5, the BA-induced gut hormones, fibroblast growth factor 19 and glucagon-like peptide 1, and the BA transport systems, apical sodium-dependent bile acid transporter and Na -taurocholate cotransporting polypeptide, within the enterohepatic circulation. Moreover, BA derivatives undergoing cholehepatic shunting may allow improved targeting to the bile ducts. This review focuses on the pathophysiological basis, mechanisms of action, and clinical development of novel pharmacological strategies targeting BA transport and signaling in cholestatic liver diseases. (Hepatology 2017;65:1393-1404).
在肠肝循环中鉴定胆汁酸（BA）合成和转运的关键调节因子，揭示了胆汁淤积性肝病药物治疗的潜在靶点。新的药物靶点包括胆汁 BA 受体、法尼醇 X 受体和 TGR5、BA 诱导的肠道激素、成纤维细胞生长因子 19 和胰高血糖素样肽 1 以及肠肝循环中的 BA 转运系统、顶端钠依赖性胆汁酸转运蛋白和 Na-牛磺胆酸钠共转运蛋白。此外，进行胆肠分流的 BA 衍生物可能允许更好地靶向胆管。这篇综述重点介绍了靶向胆汁淤积性肝病中 BA 转运和信号的新型药物策略的病理生理学基础、作用机制和临床开发。（《肝脏病学》2017；65：1393-1404）。
