孕烷X受体的研究进展

Advances in the Research of Pregame X Receptor

核受体是一类高度保守的配体依赖性转录因子家族,在哺乳动物发育、繁殖、免疫应答、心血管功能、组织生长、肿瘤形成、外源物清除及糖类和脂质代谢等生理过程中发挥重要作用。机体对外源物质的清除主要是由孕烷X受体等核受体介导的。孕烷X受体最早是作为外源物感受器而被研究的,可以被大多数亲脂性药物等外源性化合物及一些内源性化合物如胆汁酸等结构差异很大的配体激活,进而与视黄醇类X受体等形成异源二聚体,结合在ER6、XREM等DNA元件上,调控下游靶基因(包括一相代谢酶、二相结合酶及药物转运体等基因)的表达。此外,孕烷X受体在能量代谢和免疫反应中也有重要作用,参与某些代谢疾病的发生发展,且已在动物模型中被证明是Ⅱ型糖尿病、血脂异常、肥胖症和动脉粥样硬化等代谢疾病治疗的有效靶标。我们主要就其发现、结构、组织分布、作用方式、自身表达的调节等方面的最新研究进行综述。

Nuclear receptor is a highly conserved ligand-activated transcription factor functioning as critical regulators of development, reproduction, immune response, function of cardiovascular, histogenesis, tumorigenesis, carbohydrate and lipid metabolism, as well as xenobiotic clearing. The pregnane X receptor（PXR） is originally defined as xenobiotic receptor and primarily orchestrate exogenous compound metabolism. PXR can be activated by a wide spectrum of exogenous ligands including lipophilie drugs as well as endogenous molecules such as bile acids, and then conjugate with retinol X receptor（RXR） to form PXR/RXR heterodimer, which further bind to the CYP3A4 gene response elements including ER6 and XREM to regulate expression of phase Ⅰ, phase Ⅱ drug metabolizing enzymes as well as the drug transporters. Additionally, PXR also modulates energy metabolism and immune responses, as well as functions in metabolic diseases such as obesity, type Ⅱ diabetes mellitus, dyslipidemia, and atherosclerosis. This review outlined its finding, structure, tissue distribution, mode of action and regulation of expression.