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前列腺素E₂及其受体在慢性肝脏疾病中的作用研究进展

林志强¹, 姚瑶², 张羽菲³, 张晓燕¹, 管又飞^3,*

¹华东师范大学医学与健康研究院，上海 200241；²南通大学附属医院肾内科，南通 226000；³大连医科大学医学科学研究院，大连 116044

摘要

慢性肝脏疾病(chronic liver disease, CLD)是一个全球性的健康负担，其发病率和死亡率都在逐年增加。虽然多种情况可引起CLD，进而导致肝硬化和肝细胞癌，但是病毒性肝炎、药物性肝损伤、酒精性肝病和非酒精性脂肪性肝病是最常见的原因。前列腺素E2 (prostaglandin E₂, PGE₂)是ω-6多不饱和脂肪酸花生四烯酸代谢产生的一种重要脂质介质，在维持肝脏稳态平衡中起着关键作用。PGE₂通过四种不同的E型前列腺素(EP)受体，即EP1、EP2、EP3和EP4，参与机体众多生理与病理生理过程。近年来，越来越多的研究表明PGE₂和EP受体在调节肝功能和CLD的发病机制中发挥重要作用。本文将结合最新研究进展对PGE₂和EP受体在CLD中的作用进行简要综述，并讨论PGE₂-EP受体系统在治疗各种病因导致的CLD中的潜力。

关键词： 慢性肝脏疾病; 前列腺素E2; EP1; EP2; EP3; EP4

Role of prostaglandin E₂ and its receptors in chronic liver disease

LIN Zhi-Qiang¹, YAO Yao², ZHANG Yu-Fei³, ZHANG Xiao-Yan¹, GUAN You-Fei^3,*

¹Health Science Center, East China Normal University, Shanghai 200241, China；²Department of Nephrology, Affiliated Hospital of Nantong University, Nantong 226000, China；³Advanced Institute for Medical Sciences, Dalian Medical University, Dalian 116044, China

Abstract

Chronic liver disease (CLD) is a major global health burden in terms of growing morbidity and mortality. Although many conditions can cause CLD, leading to cirrhosis and hepatocellular carcinoma (HCC), viral hepatitis, drug-induced liver injury (DILI), alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) are the most common culprits. Prostaglandin E₂ (PGE₂), produced in the liver, is an important lipid mediator derived from the ω-6 polyunsaturated fatty acid, arachidonic acid, and plays a critical role in hepatic homeostasis. The physiological effects of PGE₂ are mediated through four classes of E-type prostaglandin (EP) receptors, namely EP1, EP2, EP3 and EP4. In recent years, an increasing number of studies has been done to clarify the effects of PGE₂ and EP receptors in regulating liver function and the pathogenesis of CLD to create a new potential clinical impact. In this review, we overview the biosynthesis and regulation of PGE2 and discuss the role of its synthesizing enzymes and receptors in the maintenance of normal liver function and the development and progress of CLD. We also discuss the potential of the PGE₂-EP receptors system in treating CLD with various etiologies.

Key words: chronic liver disease; prostaglandin E2; EP1; EP2; EP3; EP4

收稿日期：　　录用日期：

通讯作者：管又飞　　E-mail: guanyf@dmu.edu.cn

DOI: 10.13294/j.aps.2024.0022

引用本文：

林志强, 姚瑶, 张羽菲, 张晓燕, 管又飞. 前列腺素E₂及其受体在慢性肝脏疾病中的作用研究进展[J]. 生理学报 2024; 76 (2): 329-340.

LIN Zhi-Qiang, YAO Yao, ZHANG Yu-Fei, ZHANG Xiao-Yan, GUAN You-Fei. Role of prostaglandin E₂ and its receptors in chronic liver disease. Acta Physiol Sin 2024; 76 (2): 329-340