Cytochrome P450 (CYP) epoxygenases can metabolize arachidonic acids to epoxyeicosatrienoic acids (EETs), which play a protective role in the renal system, but their involvement in ischemia/reperfusion (I/R)-induced acute kidney injury remains unknown. Here, using a rat model, we demonstrated that forced CYP2J2 expression attenuated I/R-induced renal dysfunction and protected histological integrity. We showed that CYP2J2 significantly decreased I/R-induced upregulation of blood urea nitrogen and serum creatinine and enhanced autophagy during I/R treatment. In addition, we determined the protective effect of CYP2J2 against I/R-caused apoptosis. We demonstrated that CYP2J2 overexpression attenuated the downregulation of SIRT1 and FoxO3a by I/R-induced injury. Moreover, exogenous 11,12-EET addition obviously promoted I/R-induced autophagic flux and suppressed I/R-induced apoptosis through SIRT1-FoxO3a signaling activation. Our data indicate that CYP2J2-produced EETs improve I/R-caused kidney injury by activating the SIRT1-FoxO3a signaling pathway, which protects from renal I/R injury.

中文翻译：

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CYP2J2产生的环氧二十碳三烯酸通过激活SIRT1-FoxO3a途径减轻缺血/再灌注引起的急性肾损伤。

细胞色素P450（CYP）环氧合酶可以将花生四烯酸代谢为环氧二十碳三烯酸（EET），后者在肾脏系统中起保护作用，但它们参与缺血/再灌注（I / R）诱导的急性肾损伤的作用尚不清楚。在这里，使用大鼠模型，我们证明了强迫的CYP2J2表达减弱了I / R诱导的肾功能障碍并保护了组织学完整性。我们显示CYP2J2显着降低I / R诱导的I / R治疗期间血液尿素氮和血清肌酐的上调并增强自噬。此外，我们确定了CYP2J2对I / R引起的细胞凋亡的保护作用。我们证明CYP2J2过表达减弱了I / R诱导的损伤对SIRT1和FoxO3a的下调。而且，外生的11 12-EET的添加通过SIRT1-FoxO3a信号激活明显促进了I / R诱导的自噬通量并抑制了I / R诱导的凋亡。我们的数据表明，CYP2J2产生的EET通过激活SIRT1-FoxO3a信号传导途径来改善I / R引起的肾脏损伤，从而防止肾脏I / R损伤。