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首页> 外文期刊>American Journal of Physiology >Deletion of soluble epoxide hydrolase gene improves renal endothelial function and reduces renal inflammation and injury in streptozotocin-induced type 1 diabetes.
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Deletion of soluble epoxide hydrolase gene improves renal endothelial function and reduces renal inflammation and injury in streptozotocin-induced type 1 diabetes.

机译：可溶性环氧化物水解基因的缺失改善了肾内皮功能，减少了链脲佐菌素诱导的1型糖尿病中的肾炎和损伤。

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Studies suggest that soluble epoxide hydrolase (sEH) inhibition reduces end-organ damage in cardiovascular diseases. We hypothesize that sEH gene (Ephx2) knockout (KO) improves endothelial function and reduces renal injury in streptozotocin-induced diabetes. After 6 wk of diabetes, afferent arteriolar relaxation to acetylcholine was impaired in diabetic wild-type (WT) mice, as the maximum relaxation was 72% of baseline diameter in the WT but only 31% in the diabetic mice. Ephx2 KO improved afferent arteriolar relaxation to acetylcholine in diabetes as maximum relaxation was 58%. Urinary monocyte chemoattractant protein-1 (MCP-1) excretion significantly increased in diabetic WT mice compared with control (868 +/- 195 vs. 31.5 +/- 7 pg/day), and this increase was attenuated in diabetic Ephx2 KO mice (420 +/- 98 pg/day). The renal phospho-IKK-to-IKK ratio and nuclear factor-kappaB were significantly decreased, and hemeoxygenase-1 (HO-1) expression increased in diabetic Ephx2 KO compared with diabetic WT mice. Renal NADPH oxidase and urinary thiobarbituric acid reactive substances excretion were reduced in diabetic Ephx2 KO compared with diabetic WT mice. Albuminuria was also elevated in diabetic WT mice compared with control (170 +/- 43 vs. 37 +/- 13 mug/day), and Ephx2 KO reduced this elevation (50 +/- 15 mug/day). Inhibition of sEH using trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (tAUCB) also reduced renal inflammation and injury in diabetic WT mice. Furthermore, inhibition of HO with stannous mesoporphyrin negated the reno-protective effects of tAUCB or Ephx2 KO during diabetes. These data demonstrate that Ephx2 KO improves endothelial function and reduces renal injury during diabetes. Additionally, our data also suggest that activation of HO-1 contributes to improved renal injury in diabetic Ephx2 KO mice.
机译：研究表明，可溶性环氧化物水解酶（SEH）抑制减少了心血管疾病的末端器官损伤。我们假设SEH基因（Ephx2）敲除（KO）改善内皮功能并降低链脲佐菌素诱导的糖尿病中的肾损伤。在糖尿病6周后，在糖尿病野生型（WT）小鼠中，对乙酰胆碱的传入动脉弛豫损害，因为最大弛豫是在WT中为基线直径的72％，但糖尿病小鼠只有31％。 Ephx2 KO改善了糖尿病乙酰胆碱的传入动脉释放，因为最大弛豫是58％。与对照（868 +/- 195对31.5 +/- 7 pg /天）相比，糖尿病WT小鼠中尿性单核细胞化学蛋白-1（MCP-1）释放显着增加，并在糖尿病Ephx2 Ko小鼠中减弱这种增加（ 420 +/- 98 pg / day）。与糖尿病WT小鼠相比，肾磷酸-IKK-to-in-kap比和核因子-Kappab显着降低，糖尿病Ephx2 Ko中的血氧酶-1（HO-1）表达增加。与糖尿病WT小鼠相比，肾脏NADPH氧化酶和尿硫甲酸乙酸反应性物质排泄在糖尿病EphX2 Ko中降低。与对照相比，糖尿病WT小鼠也升高了白蛋白尿（170 +/- 43×37 +/-13杯/天），而Ephx2 Ko降低了这个升高（50 +/- 15杯/天）。使用反式-4- [4-（3-亚氨坦-1-基-Mreido） - 环己氧基] - 苯甲酸（Taucb）的抑制SEH也降低了糖尿病WT小鼠的肾炎和损伤。此外，HO与亚锡中卟啉的抑制否定了糖尿病期间Taucb或Ephx2 Ko的肾脏保护作用。这些数据表明Ephx2 KO改善内皮功能并减少糖尿病期间的肾损伤。此外，我们的数据还表明HO-1的激活有助于改善糖尿病Ephx2 KO小鼠的肾损伤。

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