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前列腺素E₂合酶及其受体在心血管疾病中的作用研究进展

刘敏, 郭美娜, 陈丽红^*

大连医科大学医学科学研究院，大连 116044

摘要

前列腺素E2 (prostaglandin E2, PGE2)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PGE2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。PGE2终末合成酶膜结合型前列腺素E2合酶-1 (microsomal prostaglandin E synthase-1, mPGES-1)及PGE2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PGE2，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。

关键词： 前列腺素E2; mPGES-1; EP受体; 心血管疾病

分类号：R363

Research advances of prostaglandin E₂ synthases and receptors in cardiovascular diseases

LIU Min, GUO Mei-Na, CHEN Li-Hong^*

Advanced Institute for Medical Sciences, Dalian Medical University, Dalian 116044, China

Abstract

Prostaglandin E2 (PGE2) 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 PGE2 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 PGE2, and the four PGE2 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 PGE2, particularly mPGES-1 and the four PGE2 receptors, in cardiovascular diseases.

Key words: prostaglandin E2; mPGES-1; EP receptors; cardiovascular disease

收稿日期：2020-12-15　　录用日期：2021-03-01

通讯作者：陈丽红　　E-mail: bjclh2000@163.com

DOI: 10.13294/j.aps.2021.0054

引用本文：

刘敏, 郭美娜, 陈丽红. 前列腺素E₂合酶及其受体在心血管疾病中的作用研究进展[J]. 生理学报 2021; 73 (4): 665-680.

LIU Min, GUO Mei-Na, CHEN Li-Hong. Research advances of prostaglandin E₂ synthases and receptors in cardiovascular diseases. Acta Physiol Sin 2021; 73 (4): 665-680 (in Chinese with English abstract).