前列腺素E_(2)及其受体在慢性肝脏疾病中的作用研究进展

Role of prostaglandin E_(2)and its receptors in chronic liver disease

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E_(2)(prostaglandin E_(2),PGE_(2))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。PGE_(2)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PGE_(2)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PGE_(2)和EP受体在CLD中的作用进行简要综述,并讨论PGE_(2)-EP受体系统在治疗各种病因导致的CLD中的潜力。

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 E_(2)(PGE_(2)),produced in the liver,is an important lipid mediator derived from theω-6 polyunsaturated fatty acid,arachidonic acid,and plays a critical role in hepatic homeostasis.The physiological effects of PGE_(2)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 PGE_(2)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 PGE_(2)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 PGE_(2)-EP receptors system in treating CLD with various etiologies.