Increased epoxyeicosatrienoic acids may be part of a protective mechanism in human ulcerative colitis, with increased CYP2J2 and reduced soluble epoxide hydrolase expression
Increased epoxyeicosatrienoic acids may be part of a protective mechanism in human ulcerative colitis, with increased CYP2J2 and reduced soluble epoxide hydrolase expression
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环氧二十碳三烯酸增加可能是人类溃疡性结肠炎保护机制的一部分，其中CYP2J2增加和可溶性环氧化物水解酶表达减少
DOI：
10.1016/j.prostaglandins.2018.03.004
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发表时间：
2018-05-01
影响因子：
2.9
通讯作者：
Zhong, Ming
中科院分区：
文献类型：
--
作者：
Qiu, Yi-Er;Qin, Jun;Zhong, Ming
背景资料：先前的临床前证据表明，源自细胞色素P450（CYP）环氧合酶依赖性花生四烯酸代谢的环氧二十碳三烯酸（EET）的升高具有重要的抗炎作用。方法：收集16对溃疡性结肠炎患者的组织活检标本，并与邻近的非炎症组织进行配对，以评估EkB及其相关的EkB亚型和代谢酶可溶性环氧化物水解酶（sEH）的表达。结果：溃疡性结肠炎组织中Escherichia coli的浓度高于相应的非炎症组织（1.91 ± 0.98 ng/mg vs.0.96 ± 0.77 ng/mg，平均SD，P < 0.01）。如免疫组化所示，sEH存在于细胞质和肠粘膜中，并且与匹配的相邻非炎症组织相比，在溃疡性结肠炎组织中显示出下降。Western blot分析显示，溃疡性结肠炎组织中sEH表达低于相应的非炎症组织（P < 0.05），而CYP 2 J2表达高于相应的非炎症组织（P < 0.05）。结论：EET水平升高可能是溃疡性结肠炎保护机制的一部分。此外，Escherichia coli的浓度可能是溃疡性结肠炎药物治疗的关键因素。
Background: Previous preclinical evidence has suggested that the elevation of epoxyeicosatrienoic acids (EETs) derived from the cytochrome P450 (CYP) epoxygenases-dependent metabolism of arachidonic acid has important anti-inflammatory effects. However, the levels of EETs and their synthetic and metabolic enzymes in human ulcerative colitis has not been evaluated.Method: To evaluate EETs and the expression of relevant CYP isoforms and the metabolizing enzyme, soluble epoxide hydrolase (sEH), tissue biopsies were collected from 16 pairs of ulcerative colitis patients' tissues and matched with adjacent non-inflamed tissues. EETs were extracted from tissue homogenates and analyzed by liquid chromatography coupled with tandem mass spectrometry.Results: The concentration of EETs was higher in ulcerative colitis tissues compared with matched adjacent non inflamed tissues (1.91 +/- 0.98 ng/mg vs. 0.96 +/- 0.77 ng/mg, mean SD, P < 0.01). As shown by immunohistochemistry, sEH was present in the cytoplasm and intestinal mucosa and showed a decline in ulcerative colitis tissues compared with matched adjacent non-inflamed tissues. Western blot analyses showed reduced sEH expression in ulcerative colitis tissues compared with matched adjacent non-inflamed tissues, whereas CYP2J2 increased in ulcerative colitis tissues (P < 0.05). However, there was no statistically significant difference observed in CYP2C8 and CYP2C9 protein expression between them (P > 0.05).Conclusion: Our data suggest that the increase in EET levels may be part of a protective mechanism in ulcerative colitis. Furthermore, the concentration of EETs could be a key factor for drug therapy for ulcerative colitis.