脂蛋白相关磷脂酶A2抑制剂Darapladib的药效学研究进展被引量：2

Pharmacodynamics Recent Advances of a Lipoprotein-associated Phospholipase A2 Specific Inhibitor Darapladib

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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。 Lipoprotein-associated phospholipase A2（ Lp-PLA2） is a member of phospholipases superfamily which can hydrolyze oxidative phospholipid in low density lipoprotein（ LDL）,and produce two proinflammatory mediators including lysophosphatidylcholine（ lyso PC） and oxidized free fatty acid.Thus,Lp-PLA2 is believed to mediate the inflammatory processes that lead to atherogenesis.Recent studies indicated that Lp-PLA2 acts as a new marker in the inflammatory process and is an independent predictor of the cardiovascular diseases.Many Lp-PLA2-targeted inhibitors have been designed to deal with the key enzyme involving in atherosclerosis.Darapladib is the specific inhibitor which is closest to the market among the rest and is drawn wide attention as an emerging therapy for atherosclerosis,and the clinical phase Ⅲ trials have been completed.Numerous experiments have confirmed that Darapladib could decrease the activity of Lp-PLA2,reduce inflammatory reaction and disrupt the development of atherosclerosis.In this paper,the authors summarized the mechanism of Lp-PLA2 and Darapladib in atherosclerosis,and the recent advances on the pharmacodynamics of Darapladib in recent years.

作者马全鑫陈民利王逸平

机构地区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

出处《中国药学杂志》 CAS CSCD 北大核心 2015年第4期317-322,共6页 Chinese Pharmaceutical Journal

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

关键词动脉粥样硬化脂蛋白相关磷脂酶A2 Darapladib atherosclerosis Lp-PLA2 Darapladib

分类号 R979.1 [医药卫生—药品]

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