可溶性环氧化物水解酶在疾病中的作用

花生四烯酸经过细胞色素P450(cytochrome P450，CYP)表氧化酶途径生成环氧二十碳三烯酸(epoxy eicosatrienoic acid，EETs)，具有扩张血管、降低血压、抗炎等多种生物学功能。在哺乳动物系统中的可溶性环氧化物水解酶（soluble epoxide hydrolase，sEH)具有α/β水解酶折叠结构，对环氧脂肪酸具有高度的选择性。sEH能够快速水解EETs，增加患心血管疾病的风险。目前，研究发现sEH抑制剂具有抑制sEH活性、提高EETs的含量的重要功能。 在多种疾病动物模型中应用sEH抑制剂或sEH基因敲除，证实sEH在心肌肥厚、糖尿病、高血压和肾病等疾病中发挥重要的生理作用。因此，sEH已被作为疾病治疗的新靶点而进行研究。本文就sEH的分布、作用机制以及sEH与疾病的关系等方面进行了讨论。

The Effects of Soluble Epoxide Hydrolase in Disease

Epoxyeicosatrienoic acids (EETs) are synthesized from arachidonic acid by cytochrome P450 epoxygenases and have many beneficial effects in metabolic diseases, including reduction of blood pressure, and inflammation in multiple species. The soluble epoxide hydrolase (sEH) in mammalian systems is a member of the α/β-hydrolase fold family and it shows a high degree of selectivity for epoxides of fatty acids. sEH readily hydrolyzes lipid signaling molecules, including EETs, epoxidized lipids produced from arachidonic acid by the action of cytochrome p450s, which leads to increased risk of cardiovascular diseases. Growing evidence suggests that sEH inhibitors can prevent sEH activity and increase the levels of EETs. Data from sEH inhibitors and knockout of sEH gene suggest a crucial role of sEH in cardiac hypertrophy, diabetes and hypertension, indicating that sEH may be a potential therapeutic target. In this review, we briefly introduced the protein structure and distribution of sEH and the function of sEH inhibitors in several disease models.