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尼曼-匹克C1型类似蛋白1影响胆固醇代谢的研究进展

杨俊瑶, 胡炎伟, 鹏, 郑磊, 王前^*

南方医科大学南方医院检验医学科，广州 510515

摘要

尼曼-匹克C1型类似蛋白1 (Niemann-Pick type C1 Like 1, NPC1L1)是一种跨膜蛋白，是尼曼-匹克C1型类似蛋白1 (Niemann-Pick type C1 Like 1, NPC1L1)是一种跨膜蛋白，是外源性胆固醇吸收的重要因子，在体内胆固醇代谢过程中发挥十分重要的作用。NPC1L1与多种脂质转运体共同影响着胆固醇的代谢。细胞核受体主要通过作用于NPC1L1启动子区域调控NPC1L1的表达，进而影响胆固醇的吸收，但其影响胆固醇吸收的具体机制还没有完全清楚。NPC1L1的表达受多种因子的调节。多不饱和脂肪酸通过甾体调节原件结合蛋白2 (sterol regulatory element binding protein 2, SREBP2)途径下调NPC1L1的表达。姜黄素及鞘氨醇等也参与NPC1L1表达的调节。降脂药物依泽替米贝(ezetimibe)可通过降低NPC1L1的表达减少胆固醇的吸收从而降低血浆胆固醇的水平，同时对其它脂类代谢病也有一定的作用。本文对NPC1L1在结构、功能和调节方面的研究进展做一综述。

关键词： 尼曼-匹克C1型类似蛋白1; 胆固醇; 依泽替米贝

分类号：R363

[Progress of Niemann-Pick type C1 Like 1 on cholesterol metabolism.] [Article in Chinese]

YANG JunYao, HU YanWei, ZHANG Peng, ZHENG Lei, WANG Qian^*

Laboratory Medicine Centre, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China

Abstract

The polytopic transmembrane protein, Niemann-Pick type C1 Like 1 (NPC1L1), is the key point of exogenous cholesterol absorption and plays an important role in cholesterol metabolism. However, the molecular mechanism of NPC1L1’s role in cholesterol uptake remains unclear. NPC1L1 expression is highly regulated by a variety of molecular actors. Nuclear receptors regulate NPC1L1 expression through its promoter region. Polyunsaturated fatty acids down-regulates NPC1L1 expression by the way of sterol regulatory element binding protein 2 (SREBP2). In addition, curcumin and sphingosine-phosphate take part in the regulation of NPC1L1 expression. NPC1L1 has been recognized as an essential protein for sterol absorption and is the molecular target of ezetimibe. Moreover, inhibition of the expression of NPC1L1 has been shown to have beneficial effects on components of the metabolic syndrome. The recent progress in the structure, function and regulation of NPC1L1 is reviewed.

Key words: Niemann-Pick type C1- Like 1; cholesterol; ezetimibe

收稿日期：2012-03-01　　录用日期：2012-06-04

通讯作者：王前　　E-mail: nfyywangqian@163.com

引用本文：

杨俊瑶, 胡炎伟, 鹏, 郑磊, 王前. 尼曼-匹克C1型类似蛋白1影响胆固醇代谢的研究进展[J]. 生理学报 2012; 64 (6): 721-728.

YANG JunYao, HU YanWei, ZHANG Peng, ZHENG Lei, WANG Qian. [Progress of Niemann-Pick type C1 Like 1 on cholesterol metabolism.] [Article in Chinese] . Acta Physiol Sin 2012; 64 (6): 721-728 (in Chinese with English abstract).