BACKGROUND Upregulation of the sodium glucose co-transporter (SGLT2) is implicated in acute renal injury (ARI) progression and is regulated by extracellular signal-regulated kinase (ERK), hypoxia-inducible factor 1 alpha (HIF1α) or prostaglandin E2 (PGE2). This study aimed to assess the possible protective effect of nebivolol on renal ischemia/reperfusion (IR) and glycerol-induced ARI targeting SGLT2 via modulating the ERK-HIF1α pathway. METHODS Rats were divided into control, sham, IR or nebivolol-treated group, in which rats were treated with nebivolol (10 mg/kg) for 3 days prior to the induction of IR. The rats were subjected to renal ischemia by bilateral clamping of the pedicles for 45 min, followed by 24 h reperfusion. Another group of rats received the vehicle or nebivolol (10 mg/kg) for 3 days followed by injection of 50% glycerol (8 ml/kg, IM) or saline. Kidney function tests, systolic blood pressure (SBP), oxidative stress markers [malondialdehyde (MDA) and NADPH oxidase] and kidney levels of nitric oxide (NO), inducible nitric oxide synthase (iNOS), HIF1α, ERK phosphorylation and PGE2 were determined. Additionally, renal sections were used for histological grading of renal injury and immunological expression of SGLT2. RESULTS ARI rats showed significantly increased SBP, poor kidney function tests, increased oxidative stress, iNOS, NO, HIF1α levels, decreased PGE2 and ERK phosphorylation and upregulation of SGLT2 expression. Nebivolol treatment protected against the kidney damage both on the biochemical and histological levels. CONCLUSION Nebivolol has a direct renoprotective effect, at least in part, by down-regulating SGLT2 possibly via modulating HIF1α, ERK activity and PGE2 production.

中文翻译：

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奈必洛尔在急性肾损伤大鼠模型中的肾脏保护作用：钠葡萄糖共转运蛋白2的作用。

背景葡萄糖共转运蛋白（SGLT2）的上调与急性肾损伤（ARI）的进展有关，并受细胞外信号调节激酶（ERK），缺氧诱导因子1α（HIF1α）或前列腺素E2（PGE2）的调节。 。这项研究旨在评估奈必洛尔通过调节ERK-HIF1α途径对肾缺血/再灌注（IR）和甘油诱导的ARI靶向SGLT2的保护作用。方法将大鼠分为对照组，假手术组，IR组或奈必洛尔治疗组，其中在IR诱导前先用奈必洛尔（10 mg / kg）处理大鼠3天。通过将双侧椎弓根夹紧45分钟，然后再灌注24 h，使大鼠经历肾脏缺血。另一组大鼠接受媒介物或奈必洛尔（10 mg / kg）3天，然后注射50％甘油（8 ml / kg，IM）或生理盐水。确定肾脏功能测试，收缩压（SBP），氧化应激指标[丙二醛（MDA）和NADPH氧化酶]以及肾脏中一氧化氮（NO），诱导型一氧化氮合酶（iNOS），HIF1α，ERK磷酸化和PGE2的水平。另外，将肾切片用于肾损伤的组织学分级和SGLT2的免疫学表达。结果ARI大鼠表现出SBP显着升高，肾功能检查不良，氧化应激，iNOS，NO，HIF1α水平升高，PGE2和ERK磷酸化降低以及SGLT2表达上调。奈必洛尔治疗可在生化和组织学水平上保护肾脏免受肾脏损害。