前列腺素E;合酶及其受体在心血管疾病中的作用研究进展  

Research advances of prostaglandin E;synthases and receptors in cardiovascular diseases

作　　者：刘敏 郭美娜 陈丽红 LIU Min;GUO Mei-Na;CHEN Li-Hong(Advanced Institute for Medical Sciences,Dalian Medical University,Dalian 116044,China)

机构地区：[1]大连医科大学医学科学研究院,大连116044

出　　处：《生理学报》2021年第4期665-680,共16页Acta Physiologica Sinica

基　　金：supported by grants from the National Natural Science Foundation of China(No.81670242,32071157)。

摘　　要：前列腺素E2(prostaglandin E_(2),PGE_(2))是花生四烯酸代谢产生的一种重要脂质介质,在人体各个组织器官广泛分布,通过结合4种不同的G蛋白耦联受体,参与机体众多生理和病理生理过程。非甾体类抗炎药(non-steroidal anti-inflammatory drugs,NSAIDs)是临床最常用的解热镇痛抗炎药,其发挥作用主要通过抑制炎症性PGE_(2)的生物合成。研究表明,长期服用NSAIDs,尤其是环氧酶-2(cyclooxygenase-2,COX-2)选择性抑制剂,会显著增加高血压、心肌梗死、心力衰竭等心血管事件的发生率,因此避免或减少心血管副作用是新型NSAIDs药物研发的主要方向。PGE_(2)终末合成酶膜结合型前列腺素E_(2)合酶-1(microsomal prostaglandin E synthase-1,mPGES-1)及PGE_(2)的4个受体EP1~EP4作为NSAIDs新靶点受到广泛关注,其在心血管疾病中的作用也备受瞩目。本文将结合最新研究进展对PGE_(2),尤其是mPGES-1和EP受体在心血管疾病中的作用进行简要综述。Prostaglandin E;(PGE;)is an important lipid mediator derived from arachidonic acid.It is widely distributed in various tissues and involved in numerous physiological and pathophysiological processes.Based on the inhibition of inflammatory PGE;production,non-steroidal anti-inflammatory drugs(NSAIDs)are considered as the most commonly used drugs to treat pain and inflammation.However,clinical trials have revealed that NSAIDs,especially cyclooxygenase-2(COX-2)selective inhibitors,may predispose patients to a remarkably increased cardiovascular risk,including hypertension,myocardial infarction,and heart failure.This promotes scientists to develop new drugs to not only afford pain relief but also have cardiovascular efficacy.Microsomal prostaglandin E synthase-1(mPGES-1),the key terminal enzyme catalyzing the synthesis of inflammatory PGE;,and the four PGE;receptors(EP1–4)have gained more attention as the promising alternative drug targets for the development of novel NSAIDs.The role of mPGES-1 and EP receptors in cardiovascular diseases also has been widely studied.In this review,we highlight the most recent advances from our and other studies on the role of PGE;,particularly mPGES-1 and the four PGE;receptors,in cardiovascular diseases.

关 键 词：前列腺素E MPGES-1 EP受体 心血管疾病 

分 类 号：R363[医药卫生—病理学]