孕烷X受体在中枢神经系统中的功能研究进展

Research Progress on Role of Pregnane X Receptor in Central Nervous System

孕烷X受体(pregnane X receptor,PXR)是核受体超家族的成员之一,其本质是配体激活型转录因子。PXR高表达于肝脏和肠道,在肾脏和脑等器官也有表达。自发现以来,PXR就被公认为是外源物质和内源物质的感受器,在激活状态下,可以调节药物代谢酶、转运蛋白和其他代谢相关蛋白质的表达,从而起到解毒等作用。由于PXR高表达于肝脏和肠道,所以其在消化系统的功能被大量研究报道。近年来,随着PXR在越来越多的脑区被检测到,其在中枢神经系统中的生理和病生理功能被广泛关注。本文主要就PXR在中枢神经系统的表达谱、在血脑屏障中的功能,以及其与神经疾病和神经毒性的关系,与行为学的相关性等进行综述。上述内容一方面可指导临床合理用药,另一方面可拓展科研工作者新药研发的思路;同时,也为未来PXR在中枢神经系统中功能的进一步研究提供了理论基础和方法思路。

As a member of the nuclear receptor superfamily,pregnane X receptor(PXR)is a ligand-activated transcription factor.It is highly expressed in liver and intestine,as well as in kidney,brain and other organs.Since its discovery,PXR has been recognized as a sensor for exogenous and endogenous substances.In the activated state,it can regulate the expression of drug-metabolizing enzymes,transporters,and other metabolism-related proteins to exert detoxification effects.Its functions in the digestive system have been intensively explored due to its high expression in liver and intestine.In recent years,with the detection of PXR in more and more brain regions,its physiological and pathophysiological functions in the central nervous system have attracted much attention.This review summarized the expression profile of PXR in the central nervous system,its role in the blood-brain barrier,its relationship with neurological diseases and neurotoxicity,and its correlation with the behavioral science.The summary may provide guidance on clinical medication and new ideas for drug development,and also be beneficial for future research on PXR functions in the central nervous system.