基于高密度脂蛋白的抗动脉粥样硬化小分子药物研究现状  

Research progress in small molecule drugs based on high-density lipoprotein for anti-atherosclerosis

作　　者：马贝贝 卞聪 洪斌[1] 杜郁[1] 陈晓芳[1] 

机构地区：[1]中国医学科学院北京协和医学院医药生物技术研究所,北京100050

出　　处：《药学学报》2018年第3期328-335,共8页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金青年基金资助项目(81402929);北京市自然科学基金面上资助项目(7162129)

摘　　要：大量流行病学结果显示,高密度脂蛋白胆固醇水平与动脉粥样硬化性心血管疾病发病率呈负相关,提示高密度脂蛋白可能具有抗动脉粥样硬化的作用。可能机制包括促进胆固醇逆转运、抗炎、抗氧化及对抗血栓和促纤溶作用等多个途径,其中,胆固醇逆转运可能在保持胆固醇平衡、缓解动脉粥样硬化病程中发挥了重要作用。载脂蛋白A-I、ATP结合盒转运子A1、肝脏X受体及胆固醇酯转运蛋白等多种蛋白因子在逆转运过程中扮演了重要角色,这些可能是基于高密度脂蛋白的药物发现的潜在靶点。因而,本文将以这几个关键蛋白为基础对抗动脉粥样硬化小分子药物研究现状进行综述。A large number of epidemiological data have shown that the high-density lipoprotein cholesterol level is negatively related to atherosclerotic cardiovascular disease, suggesting that high-density lipoprotein may have the effect of anti-atherosclerosis. It may play the role of anti-atherosclerosis, through the promotion of cholesterol reverse transport, anti-inflammatory, antioxidant, and against thrombosis and fibrinolysis and so on. Among them, reverse cholesterol transport which is mainly regulated by apolipoprotein A-I, ATP-binding cassette transporter 1, liver X receptor and cholesteryl ester transfer protein, may play a major role in the maintenance of cholesterol homeostasis and reversing the course of atherosclerosis. These regulatory factors may be potential targets in high density lipoprotein-based drug discovery. In this review, these key proteins are discussed for the current status of small molecule drugs against atherosclerosis.

关 键 词：高密度脂蛋白 动脉粥样硬化 胆固醇逆转运 载脂蛋白A-I ATP结合盒转运子A1 肝脏X受体 胆固醇酯转运蛋白抑制剂 

分 类 号：R966[医药卫生—药理学]