可溶性环氧化物水解酶脲类抑制剂的研究进展

可溶性环氧化物水解酶(Soluble epoxide hydrolases,sEH)是一种能代谢环氧脂肪酸的酶,它在哺乳动物中广泛存在,能将内源性环氧二十碳三烯酸(Epoxyeicosatrienoic acids or EETs)转化为二羟基二十碳三烯酸(Dihydroxy epoxyeicosatrienoic acids or DHETs)。内源性EETs是由花生四烯酸(Arachidonic acid or AA)经细胞色素P450氧化而来,它是生物体内重要的信号分子,具有调节离子转运和基因表达、血管扩张、抗炎等作用。在动物体内,有很多种途径可以降解EETs,其中sEH将EETs代谢为DHETs是最主要的代谢途径,使EETs的浓度降低,生理活性下降,从而使体内的血压升高,并进一步影响肾脏,心脏等功能。研究表明,抑制sEH的活性可治疗多种心血管疾病及炎症。因此开发新型sEH的抑制剂在治疗相关疾病中具有很好的应用价值。主要概述了sEH的抑制剂的作用机理以及抑制剂研究的最新进展,并展望了抑制剂今后的研究方向。

Progress on the Research of Urea Inhibitors of Soluble Epoxide Hydrolase

Soluble epoxide hydrolase(sEH) is an enzyme that can metabolize epoxy fatty acids.It is widespread in mammals,and can metabolize endogenous epoxyeicosatrienoic acids(EETs) into dihydroxy epoxyeicosatrienoic acids(DHETs).Endogenous EETs,a kind of important signal molecules in vivo,come from the oxidation of arachidonic acids(AA) with cytochrome P450.EETs can regulate the ion transport and gene expression,vasodilatation and anti-inflammatory.In vivo,among the various pathways of degradation of the endogenous EETs,the conversion of EETs into DHETs caused by the sEH is of the most importance.The degradation of EETs results in decreasing of the concentration and the physiological activity of EETs,therefore increases the blood pressure,which further affects the kidneys,heart and other functions.Studies have shown that inhibiting the activity of sEH can treat various cardiovascular diseases and inflammation.This review described the resources,distribution and action mechanism of sEH inhibitors,and their future prospects.