花生四烯酸细胞色素P450代谢物在肾脏生理和疾病中的作用
方琴, 陈光志, 王炎, 汪道文^*
华中科技大学同济医学院附属同济医院心内科，心血管病遗传与分子机制湖北省重点实验室，高血压病研究所，武汉430030
摘要
肾脏疾病在全球范围内都是导致死亡的重要原因。肾脏微血管功能失调在肾病的发生与发展中发挥着不可忽视的作用。药理学和生物化学等领域的许多实验方法已被用来研究花生四烯酸的细胞色素P450 (cytochrome P450, CYP450)代谢物对肾脏微血管功能的调控作用。在肾脏中，CYP450表氧化酶代谢物环氧二十碳三烯酸(epoxyeicosatrienoic acids, EETs)主要在肾脏微血管产生。EETs可以通过舒张血管、降低血压、抗细胞凋亡、抗炎等多个方面发挥肾脏保护作用。CYP450表氧化酶代谢物EETs可作为肾脏疾病的治疗靶点。然而，在肾脏发生疾病时，肾脏微血管产生EETs的能力会显著降低。近来，用转基因动物过表达CYP450表氧化酶或用可溶性环氧化物水解酶(soluble epoxide hydrolase, sEH)抑制剂也均证实增加EETs水平具有明显的肾脏保护作用。本综述将重点讨论花生四烯酸的CYP450代谢物EETs在肾脏生理及疾病状态下具体的调控机制。
关键词： 细胞色素P450代谢物; 环氧二十碳三烯酸; 肾脏疾病
分类号：R334

Role of cytochrome P450 epoxygenase-dependent arachidonic acid metabolites in kidney physiology and diseases
FANG Qin, CHEN Guang-Zhi, WANG Yan, WANG Dao-Wen^*
Division of Cardiology, Departments of Internal Medicine and Institute of Hypertension, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders (Huazhong University of Science and Technology), Wuhan 430030, China
Abstract
Kidney diseases are important causes of mortality world widely. Renal microvascular dysfunction plays a pivotal role in the development of kidney diseases. Pharmacological and biochemical tools have been used to conduct detailed studies on the metabolization of arachidonic acid by cytochrome P450 (CYP450) in renal microvasculature. CYP450 epoxygenase metabolites epoxyeicosatrienoic acids (EETs) are mainly produced in renal microvessels. EETs exhibit renoprotective effects through vasodilation, anti- hypertension, anti-apoptosis and anti-inflammation, and were reported as therapeutic targets of renal diseases. However, the ability of the kidney in generating EETs is reduced in renal diseases. Recently, the studies from transgenic animal overexpressing CYP450 epoxygenases and application of soluble epoxide hydrolase inhibitors revealed that increasing of EETs exhibits renoprotective effects in vivo. The present review focuses on the protective mechanisms of EETs in kidney physiology and diseases.


Key words: cytochrome P450 (CYP450) epoxygenase; epoxyeicosatrienoic acid (EET); kidney disease

收稿日期：2018-05-16　　录用日期：2018-07-30
通讯作者：汪道文　　E-mail: dwwang@tjh.tjmu.edu.cn
DOI: 10.13294/j.aps.2018.0074
引用本文：
方琴, 陈光志, 王炎, 汪道文. 花生四烯酸细胞色素P450代谢物在肾脏生理和疾病中的作用[J]. 生理学报 2018; 70 (6): 591-599.
FANG Qin, CHEN Guang-Zhi, WANG Yan, WANG Dao-Wen. Role of cytochrome P450 epoxygenase-dependent arachidonic acid metabolites in kidney physiology and diseases. Acta Physiol Sin 2018; 70 (6): 591-599



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