胆汁酸肠肝循环转运蛋白及FXR对其的调控机制

胆汁酸作为胆汁的重要成分，由肝以胆固醇为原料进行合成，能在外源食物及相关激素的刺激下与胆汁一同被排入消化道内，具有脂肪乳化、促进肠道吸收脂质、调节肝肠功能、增加能量消耗、改善胰岛素敏感性等作用，一般可通过经典途径和替代途径两种方式进行合成。肠肝循环能将从头合成的胆汁酸重新回收约95%，仅剩余5%会流失，经替代途径进行再补充，从而保障了胆汁酸池的动态平衡，因此，肠肝循环在调节胆汁酸稳态等方面具有重要作用。近年来，随着研究的深入，胆汁酸的代谢与运输机制逐渐明确，参与肠肝循环的转运蛋白功能也更加清晰，其中，法尼酯X受体（FXR）作为重要的核因子能通过与小异二聚体受体（SHP）、视黄酸受体α（RARα）等，联合成纤维细胞生长因子15/19（FGF15/19）对胆汁酸转运蛋白的表达量进行调控，进而影响胆汁酸稳态。本文将对胆汁酸肠肝循环过程中涉及到的重要转运蛋白及FXR对其的调节机制进行阐述，为今后进一步探究胆汁酸功能提供一定的理论基础。

Bile Acid Enterohepatic Circulation Transporter and Its Regulatory Mechanism by FXR

As an important component of bile, bile acid is synthesized by the liver using cholesterol as a raw material. It can be excreted into the digestive tract together with bile under the stimulation of exogenous food and related hormones. Bile acids can emulsify fat, promote intestinal absorption of lipids, and regulate liver and intestine functions, increasing energy consumption, improve insulin sensitivity. The bile acid, generally can be synthesized in two ways, the classical route and the alternative route. The enterohepatic circulation can recycle about 95% of the bile acids synthesized from the beginning, and only 5% which can be refilled through alternative ways to ensure the dynamic balance of the bile acid pool will be lost. Therefore, the enterohepatic circulation plays a vital role in regulating the homeostasis of bile acids. With the deepening of research, the metabolism and transport mechanisms of bile acids have been gradually clarified, and the functions of transporters involved in the enterohepatic circulation have become more clear in recent years. The farnesoid X receptor (FXR), as an important nuclear factor, can regulate the expression of bile acid transporter through small heterodimer receptor (SHP), retinoic acid receptor α (RARα), combined with fibroblast growth factor 15/19 (FGF15/19), and then affects bile acids homeostasis. This article describes the significant transporters involved in the enterohepatic circulation of bile acids and the regulatory mechanism of FXR, which will provide a theoretical basis for further exploration of bile acid functions in the future.