2型糖尿病中环氧二十碳三烯酸代谢的改变及其与视网膜病变进展的潜在关联
Alterations in Epoxyeicosatrienoic Acids Metabolism in Type 2 Diabetes Mellitus and Potential Association with Retinopathy Progression.
摘要(中文译文)
由细胞色素P450环氧化酶（主要为CYP2C9、CYP2J2和CYP2S1）合成的环氧二十碳三烯酸（EETs）是具有血管保护作用的脂质介质，可被可溶性环氧化物水解酶（sEH）快速降解。本研究旨在检测伴或不伴糖尿病视网膜病变（DR）的2型糖尿病（T2DM）患者中EET代谢的变化，以了解其在疾病发病机制和进展中的潜在作用。研究纳入200例T2DM患者（不伴DR）、100例非增殖性DR（NPDR）患者、100例增殖性DR（PDR）患者以及200例匹配的健康对照者。采用LC-MS/MS定量检测血浆EET水平，并分别采用qPCR和ELISA检测CYP2J2、CYP2C9、CYP2S1和sEH的mRNA及蛋白水平。与对照组、不伴DR的T2DM组及NPDR组相比，PDR患者的EET水平显著升高（p < 0.05）。相反，不伴DR的T2DM组和NPDR组的EET水平明显低于对照组，但差异无统计学意义。在这两组中，CYP2J2和CYP2S1的mRNA和/或蛋白水平显著降低，提示EET生物合成受到抑制。然而，NPDR组和PDR组的CYP2C9蛋白水平高于对照组。此外，在NPDR与PDR的比较中，PDR组的CYP2J2和CYP2S1 mRNA水平较高，而CYP2C9和EPHX2表达无显著差异。与健康对照者相比，不伴DR的T2DM组和NPDR组的血浆EET浓度呈降低趋势，但差异未达到统计学显著性。相反，PDR患者的EET水平显著升高，提示DR进展过程中EET代谢存在阶段依赖性改变。EET代谢的改变可能在DR中发挥双重作用，既影响早期微血管损伤，又影响晚期血管生成进展。
Abstract
Epoxyeicosatrienoic acids (EETs), synthesized by cytochrome P450 epoxygenases (mainly CYP2C9, CYP2J2, and CYP2S1), are vasoprotective lipid mediators that are rapidly degraded by soluble epoxide hydrolase (sEH). This study aimed to examine changes in EET metabolism in T2DM patients with and without DR to understand its potential role in disease pathogenesis and progression. Two hundred T2DM patients (without DR), 100 with non-proliferative DR (NPDR), 100 with proliferative DR (PDR), and 200 matched healthy controls were enrolled in the study. Plasma EET levels were quantified using LC-MS/MS, and mRNA and protein levels of CYP2J2, CYP2C9, CYP2S1, and sEH were measured using qPCR and ELISA, respectively. Compared to the controls, T2DM without DR and NPDR groups, patients with PDR had significantly higher EET levels (p < 0.05). In contrast, the T2DM without DR and NPDR groups exhibited remarkably lower EET levels than controls, although this was not significant. In both groups, CYP2J2 and CYP2S1 mRNA and/or protein levels were significantly lower, suggesting suppressed EET biosynthesis. However, CYP2C9 protein levels were higher in NPDR and PDR groups than in the control group. Furthermore, in the comparison between NPDR and PDR, CYP2J2 and CYP2S1 mRNA levels were higher in PDR, whereas CYP2C9 and EPHX2 expression did not differ significantly. Plasma EET concentrations showed a tendency to be lower in the T2DM without DR and NPDR groups compared with healthy controls; however, these differences did not reach statistical significance. In contrast, patients with PDR exhibited significantly higher EET levels, suggesting stage-dependent alterations in EET metabolism during the progression of DR. Altered EET metabolism may play a dual role in DR, influencing both early microvascular impairment and late-stage angiogenic progression.
如何引用
AMA
İsmail Sarı, Esma Özmen, Kürşad Ramazan Zor, Serpil Erşan, Erkut Küçük, Durmuş Ayan, et al. Alterations in Epoxyeicosatrienoic Acids Metabolism in Type 2 Diabetes Mellitus and Potential Association with Retinopathy Progression.. Current medicinal chemistry. 2026; doi:10.2174/0109298673474072260623040834.
APA
İsmail Sarı, Esma Özmen, Kürşad Ramazan Zor, Serpil Erşan, Erkut Küçük, Durmuş Ayan, et al (2026). Alterations in Epoxyeicosatrienoic Acids Metabolism in Type 2 Diabetes Mellitus and Potential Association with Retinopathy Progression.. Current medicinal chemistry. https://doi.org/10.2174/0109298673474072260623040834
GB/T 7714
İsmail Sarı, Esma Özmen, Kürşad Ramazan Zor, Serpil Erşan, Erkut Küçük, Durmuş Ayan, et al. Alterations in Epoxyeicosatrienoic Acids Metabolism in Type 2 Diabetes Mellitus and Potential Association with Retinopathy Progression.[J]. Current medicinal chemistry, 2026 doi:10.2174/0109298673474072260623040834.
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