Background Hyperoxia (HO) causes kidney injury in preterm infants; however, whether these effects are modifiable is unknown. We hypothesized that administration of exogenous soluble Klotho, a kidney-derived antioxidant, would attenuate HO-induced kidney injury during postnatal nephrogenesis in rats. Methods Sprague Dawley neonatal rats assigned to normoxia (21% O 2 ) or HO (85% O 2 ) groups from postnatal day (P) 1 to 21 were randomly assigned to receive alternate day intraperitoneal injections of recombinant Klotho or placebo for 3 weeks. They were recovered in normoxia for an additional 3 weeks and sacrificed at 6 weeks. Renal artery resistance and pulsatility indices, tubular injury scores, glomerular area, and renal antioxidant capacity were assessed. Results Rodents exposed to HO during postnatal nephrogenesis had reduced kidney Klotho expression, glomerulomegaly, and higher tubular injury scores. Exogenous Klotho administration improved renal perfusion as indicated by decreases in both resistance and pulsatility indices and increased antioxidant enzyme expression. Conclusions HO exposure during postnatal nephrogenesis in rodents results in a decline in kidney Klotho expression, decreased renal perfusion, enlarged glomerular size, and tubular injury. The exogenous administration of Klotho attenuated HO-induced kidney injury and augmented antioxidant capacity.

中文翻译：

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Klotho 补充剂对啮齿动物产后肾发生模型高氧肾损伤的影响

背景 高氧 (H2O) 会导致早产儿肾损伤；然而，这些影响是否可以改变是未知的。我们假设外源性可溶性 Klotho（一种肾源性抗氧化剂）的给药会减轻大鼠出生后肾形成过程中 H2O 引起的肾损伤。方法 Sprague Dawley 新生大鼠从出生后第 1 天（P）到第 21 天被分配到常氧（21% O 2 ）或 H O（85% O 2 ）组，随机分配接受重组 Klotho 或安慰剂隔日腹腔注射 3 周。它们在常氧环境中再恢复 3 周，并在 6 周时处死。评估了肾动脉阻力和搏动指数、肾小管损伤评分、肾小球面积和肾抗氧化能力。结果在出生后肾形成过程中暴露于 H2O 的啮齿动物降低了肾脏 Klotho 表达、肾小球肿大和较高的肾小管损伤评分。外源性 Klotho 给药改善了肾脏灌注，表现为阻力和搏动指数降低以及抗氧化酶表达增加。结论 啮齿动物出生后肾形成过程中 H2O 暴露导致肾脏 Klotho 表达下降、肾灌注减少、肾小球增大和肾小管损伤。Klotho 的外源性给药减轻了 H2O 诱导的肾损伤并增强了抗氧化能力。结论 啮齿动物出生后肾形成过程中 H2O 暴露导致肾脏 Klotho 表达下降、肾灌注减少、肾小球增大和肾小管损伤。Klotho 的外源性给药减轻了 H2O 诱导的肾损伤并增强了抗氧化能力。结论 啮齿动物出生后肾形成过程中 H2O 暴露导致肾脏 Klotho 表达下降、肾灌注减少、肾小球增大和肾小管损伤。Klotho 的外源性给药减轻了 H2O 诱导的肾损伤并增强了抗氧化能力。