肝X受体调控脂代谢研究进展  

Research progress in regulation of lipid metabolism by liver X receptors

作　　者：韩汶润 张丹丹[1,2] 朱彦 杜晓鹂[1,2] 董鹏志 HAN Wen-run;ZHANG Dan-dan;ZHU Yan;DU Xiao-li;DONG Peng-zhi(State Key Laboratory of Component-based Chinese Medicine,Tianjin University of Traditional Chinese Medicine,Tianjin 301608,China;Chinese Medicine New Drug Research and Development Center,Tianjin International Joint Academy of Biomedicine,Tianjin 300457,China)

机构地区：[1]天津中医药大学组分中药国家重点实验室,天津301608 [2]天津国际生物医药联合研究院中药新药研发中心,天津300457

出　　处：《中国药理学与毒理学杂志》2021年第5期391-400,共10页Chinese Journal of Pharmacology and Toxicology

基　　金：国家重点研发计划(2018YFC1704502);国家重点基础研究发展计划(973计划)(2014CB542902)。

摘　　要：肝X受体(LXR)属于核受体家族成员,通过与类视黄醇X受体结合形成异二聚体,调控靶基因的表达。LXR是胆固醇和脂质代谢的重要调节因子,通过调控其靶蛋白ATP结合盒转运蛋白A1、ATP结合盒转运蛋白G1和细胞色素P4507A1等促进胆固醇逆转运。此外,LXR激动剂能够调控脂质代谢及炎症介质基因的表达,改善糖代谢,从而发挥抗动脉粥样硬化作用,是治疗心血管疾病的潜在药物靶标。经典的LXR合成类激动剂有T0901317和GW3965等,动物实验结果表明其可减缓动脉粥样硬化,但由于易引发脂肪肝和高甘油三酯血症等不良反应,其应用受到限制。本文就LXR生理机制及其合成与天然产物配体的研究进展进行综述,以期促进对LXR的认知,并为其研究提供新思路。The liver X receptor(LXR)is a member of the nuclear receptor family,which forms a heterodimer by binding to the retinoid X receptor to regulate the expression of target genes.LXR is an important regulator of cholesterol and lipid metabolism,and promotes reverse cholesterol transport by regulating its target proteins—ATP-binding cassette transporter A1,ATP-binding cassette transporter G1 and cytochrome P4507 A1,etc.In addition,LXR agonists can regulate lipid metabolism and the expressions of inflammatory mediator genes,improve glucose metabolism,and thus exert an anti-atherosclerotic effect.It is a potential drug target for the treatment of cardiovascular diseases.Classic LXR synthetic agonists include T0901317 and GW3965,which have been proven to slow atherosclerosis in preclinical animal experiments,but their application is limited by such side effects as fatty liver and hypertriglyceridemia.Therefore,this article reviews the research on the physiological mechanism of LXR and its synthesis and natural product ligands in order to advance our understanding of LXR and provide new ideas for related research.

关 键 词：肝X受体 动脉粥样硬化 胆固醇逆转运 肝X受体配体 

分 类 号：R963[医药卫生—微生物与生化药学]