胆固醇7α-羟化酶在胆汁淤积中的调节机制研究进展

Research progress on regulatory mechanisms of cholesterol 7α-hydroxylase in cholestasis

胆汁淤积是由多种原因所致的胆汁酸异常积聚,临床表现为黄疸或黄斑瘤等。胆固醇7α-羟化酶(cholesterol 7α-hydroxylase,CYP7A1)是体内催化胆固醇合成胆汁酸的限速酶,其活性与胆汁酸的合成量密切相关。机体中由法尼酯衍生物X受体(FXR)介导的法尼酯衍生物X受体/小异二聚体伴侣(FXR/SHP)信号通路和法尼酯衍生物X受体/成纤维细胞因子19/成纤维生长因子受体4(FXR/FGF19/FGFR4)信号通路以及由孕甾烷X受体(PXR)介导的信号通路是重要的胆固醇7α-羟化酶调节路径。上述通路通过调节胆固醇7α-羟化酶的活性,调控胆汁酸的合成,进而维持胆汁酸的内平衡。本文就近年来有关胆汁淤积中胆固醇7α-羟化酶的调节机制研究进行综述,为探索临床治疗胆汁淤积的靶点提供了参考。

Cholestasis is an abnormal accumulation of bile acids caused by various causes,and the clinical manifestations are jaundice or macular tumors.Cholesterol 7α-hydroxylase (CYP7A1) is the rate-limiting enzyme which catalyzes the synthesis of bile acids from cholesterol.Its activity is closely related to the amount of bile acid synthesis.FXR-mediated FXR/SHP signaling pathway and FXR/FGF19/FGFR4 signaling pathway,and PXR-mediated signaling pathway are important CYP7A1 regulatory pathways in vivo.The above signaling pathways regulate the synthesis of bile acids by regulating the activity of CYP7A1,thus maintain the internal balance of bile acids.This review introduced the research progress of regulatory mechanisms of CYP7A1 in cholestasis in recent years,and provided references for exploring the targets of clinical treatment of cholestasis.