脂蛋白相关磷脂酶A2抑制剂Darapladib的药效学研究进展

发布时间：2018-06-15 20:15

本文选题：动脉粥样硬化 + 脂蛋白相关磷脂酶A　；参考：《中国药学杂志》2015年04期

【摘要】：脂蛋白相关磷脂酶A2(lipoprotein-associated Phospholipase A2,Lp-PLA2)是磷脂水解酶超家族中的一员,能水解低密度脂蛋白中的氧化修饰磷脂,产生溶血卵磷脂和氧化性游离脂肪酸两种促炎介质。最近研究发现Lp-PLA2能够介导炎症反应以及促进动脉粥样硬化(atherosclerosis,AS)的形成,现已成为一个新炎性反应标志物和心血管事件的独立风险预示因子。针对这一动脉粥样硬化过程中的关键酶设计的抑制剂很多。其中Darapladib是目前最接近上市的一种Lp-PLA2特异性抑制剂,目前其Ⅲ期临床试验已完成。Darapladib作为一种新兴的抗AS分子靶点药物,受到人们广泛的关注。已有多项研究表明它能降低Lp-PLA2的活性,减轻炎症反应,从而控制AS的发展与恶化。本文综述了Lp-PLA2及其抑制剂Darapladib在AS中的作用机制以及近年来Darapladib的药效学研究进展。
[Abstract]:Lipoprotein related phospholipase A2 (lipoprotein-associated Phospholipase A2, Lp-PLA2), a member of the phosphatidic hydrolase superfamily, can hydrolyze oxidized phospholipids from low density lipoproteins and produce two kinds of proinflammatory mediators, hemolytic lecithin and oxidative free fatty acids. Recently, Lp-PLA2 has been found to mediate inflammatory reactions and promote activity. The formation of atherosclerosis (AS) has now become an independent risk predictor of a new inflammatory response marker and cardiovascular event. There are many inhibitors designed for the key enzymes in this atherosclerosis. Among them, Darapladib is one of the most closely related Lp-PLA2 specific inhibitors at present, and is currently in stage III The clinical trial has completed.Darapladib as a new anti AS molecular target drug, which has attracted wide attention. Many studies have shown that it can reduce the activity of Lp-PLA2, reduce the inflammatory reaction and control the development and deterioration of AS. This paper summarizes the mechanism of Lp-PLA2 and its inhibitor Darapladib in AS and the Dara in recent years. Progress in the pharmacodynamics of pladib.
【作者单位】：浙江中医药大学动物实验研究中心/比较医学研究中心;中科院上海药物研究所;
【基金】：国家科技重大专项子课题(2012zx09103101-008) “浙江省卫生高层次创新人才培养工程项目”资助
【分类号】：R96

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