有机溶质转运体α/β参与胆汁酸代谢的研究进展

Research progress of organic solute transporterα/βin bile acid metabolism

肠肝循环是体内胆汁酸代谢过程中至关重要的一环。目前,多个在其中发挥重要功能的胆汁酸转运体已被发现,包括回肠顶端膜刷状缘吸收胆汁酸的顶膜钠离子依赖性胆汁酸转运体(apical sodiumdependent bile acid transporter,ASBT)[1]和肝细胞摄取胆汁酸的钠离子-牛磺胆酸共转运多肽(Na-tauro⁃cholate co-transporting polypeptide,NTCP)[2]等。本世纪初,研究者发现了一种在肠上皮细胞基侧膜控制胆汁酸分泌至门静脉血流的新型胆汁酸转运体,并命名为有机溶质转运体α/β(organic solute trans⁃porterα/β,OSTα/β)。OSTα/β由OSTα和OSTβ两个亚基组成,且只有OSTα和OSTβ同时表达时才能稳定存在并发挥功能[3-5]。小鼠OSTα缺乏会导致肠道绒毛变钝、融合以及胆汁酸吸收不良等表型[6]。

The organic solute transporter α/β(OSTα/β)is a recently discovered transporter that controls bile acid secretion into portal blood stream in the basal lateral membrane of intestinal epithelial cells.OSTα/β is a compound composed of 2 subunits,OSTα and OSTβ.Only when the 2 subunits are expressed at the same time,they exist stably and function properly.It is responsible for the transmembrane transport of organic solutes such as bile acids in a way of easy diffusion.OSTα/β is regulated by bile acid receptor,also named as farnesoid X receptor(FXR).Studies showed that the bile acid synthesis in OSTα deficient mice is decreased,while the bile acid content in the urine is increased.It is worth mentioning that the single gene mutation leads to OSTβ deficiency in the patients with clinical symptoms such as chronic diarrhea and cholestatic liver disease.This paper reviews the structure,function and role of OSTα/β in enterohepatic circulation and the diseases caused by loss of OSTα/β.