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花生四烯酸的细胞色素P450酶代谢途径产物EETs和20-HETE在血管功能调控中的作用

赖金胜^1,2, 陈琛^1,2,*

¹华中科技大学同济医学院附属同济医院心血管内科，武汉 430030；²湖北省心血管病遗传与分子机制重点实验室，武汉 430030

摘要

花生四烯酸(arachidonic acids, AA)广泛存在于生物体内，并可通过多种途径代谢成为具有强大生物学功能的脂质小分子。其中，经细胞色素P450酶代谢途径产生的环氧二十碳三烯酸(epoxyeicosatrienoic acids, EETs)及20-羟基二十碳四烯酸(20-hydroxyeicosatetraenoic acid, 20-HETE)的作用备受关注，尤其是在血管稳态中的作用。血管功能调控是维持血管稳态的基础，主要通过对血管的结构和(或)生物学活性的影响而实现。近30年来，EETs及20-HETE在血管功能调控中的作用及机制被广泛研究。本文分别就EETs和20-HETE在血管新生和血管炎症反应等方面的研究进展逐一进行综述。总的来说，在生物学活性方面，EETs主要体现为舒张血管和抑制血管炎症，而20-HETE则可以促进血管收缩和血管炎症。两者在血管新生方面的作用类似，都可以促进血管新生。另外，本文还对EETs和20-HETE在常见的血管性疾病(如高血压和心肌缺血)中的作用进行了探讨，对其中的作用机制进行了分析和总结，并对基于EETs和20-HETE的血管性疾病靶向治疗提出了展望。

关键词： 花生四烯酸; 细胞色素P450酶; EETs; 20-HETE; 血管功能; 血管性疾病

分类号：Q74; R543

The roles of cytochrome P450 metabolites of arachidonic acid in the regulation of vascular function

LAI Jin-Sheng^1,2, CHEN Chen^1,2,*

¹Division of Cardiology, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, China；²Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiologic Disorders, Wuhan 430030, China

Abstract

Arachidonic acids (AA) widely exist in multiple organs and can be metabolized into small lipid molecules with strong biological functions through several pathways. Among them, epoxyeicosatrienoic acids (EETs) and 20-hydroxyeicosatetraenoic acid (20-HETE), which are produced by cytochrome P450 enzymes, have attracted a lot of attentions, especially in vascular homeostasis. The regulation of vascular function is the foundation of vascular homeostasis, which is mainly achieved by manipulating the vascular structure and biological function. In the past 30 years, the roles of EETs and 20-HETE in the regulation of vascular function have been widely explored. In this review, we discussed the effects of EETs and 20-HETE on angiogenesis and vascular inflammation, respectively. Generally, EETs can dilate blood vessels and inhibit vascular inflammation, while 20-HETE can induce vasoconstriction and vascular inflammation. Interestingly, both EETs and 20-HETE can promote angiogenesis. In addition, the roles of EETs and 20-HETE in several vascular diseases, such as hypertension and cardiac ischemia, were discussed. Finally, the therapeutic perspectives of EETs and 20-HETE for vascular diseases were also summarized.

Key words: arachidonic acid; cytochrome P450; EETs; 20-HETE; vascular function; vascular diseases

收稿日期：2021-02-20　　录用日期：2021-05-25

通讯作者：陈琛　　E-mail: chenchen@tjh.tjmu.edu.cn

DOI: 10.13294/j.aps.2021.0059

引用本文：

赖金胜, 陈琛. 花生四烯酸的细胞色素P450酶代谢途径产物EETs和20-HETE在血管功能调控中的作用[J]. 生理学报 2021; 73 (4): 631-645.

LAI Jin-Sheng, CHEN Chen. The roles of cytochrome P450 metabolites of arachidonic acid in the regulation of vascular function. Acta Physiol Sin 2021; 73 (4): 631-645 (in Chinese with English abstract).