胆固醇代谢紊乱及其相关疾病的研究进展

The progress of genetics of cholesterol metabolism disorder and its related diseases

胆固醇是生命活动必不可少的脂类物质,胆固醇浓度过高或者过低均对人体有害。但由体内胆固醇水平过高引起高胆固醇血症,是导致动脉粥样硬化、脑中风和冠心病的重要危险因素之一。人体内胆固醇有两种来源:以乙酰辅酶A为原料从头合成,或者通过小肠从食物中吸收。现今,过量的胆固醇摄取是引起高胆固醇血症的重要原因。胆固醇在小肠中的吸收是一个复杂的、多步骤的连续分解、转运以及重新酯化的过程。其中Niemann-Pick C1 Like 1(NPC1L1)蛋白介导肠道中胆固醇进入血液,是胆固醇吸收的限速步骤。胆固醇转运蛋白(CETP)介导血浆脂蛋白之间胆固醇的转运,在胆固醇逆转运过程中发挥关键作用。研究表明抑制外源性胆固醇的吸收和转运能够较好地降低血液中胆固醇的浓度,有效预防和降低心血管疾病的发生。本文重点总结了胆固醇代谢紊乱的相关疾病和肠道胆固醇吸收的分子途径、调控机制、药物研发现状。

Cholesterol is an essential lipid with many physiological functions .Cholesterol concentration is too high or too low both are harmful to human body .High level of cholesterol is called hypercholesterolemia which is a major risk factor for atherosclerosis , stroke and heart disease .The humans obtain cholesterol through de novo synthesis from acetyl-CoA and intestinal absorption from food.In developing societies , excessive cholesterol absorption is an important reason of hypercholesterolemia .Intestinal cholesterol absorption is a sophisticated process including hydrolysis , transport and re-esterification.Niemann-Pick C1 Like 1 （ NPC1L1） facili-tates cholesterol entering enterocytes that is the rate-limiting step.This review summarizes cholesterol metabolism disorder related diseases , the molecular pathway and regulation of intestinal cholesterol absorption , and development of cholesterol absorption inhibi-tors.