Division of Pediatric Nephrology, University of Miami Miller School of Medicine, Miami, FL, USA.
Division of Neonatology, University of Miami Miller School of Medicine, Miami, FL, USA.
Pediatr Res. 2020 Oct;88(4):565-570. doi: 10.1038/s41390-020-0803-z. Epub 2020 Feb 14.
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.
Sprague Dawley neonatal rats assigned to normoxia (21% O) or HO (85% O) 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.
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.
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.
高氧（HO）可导致早产儿的肾脏损伤；然而，这些影响是否可以改变尚不清楚。我们假设，在新生肾发生期间，给予外源性可溶性 Klotho（一种肾脏来源的抗氧化剂），可以减轻 HO 引起的肾脏损伤。
将新生 Sprague Dawley 大鼠分配到正常氧（21% O）或高氧（85% O）组，从出生后第 1 天到第 21 天，随机接受重组 Klotho 或安慰剂的隔日腹腔注射，持续 3 周。然后在正常氧下恢复 3 周，并在 6 周时处死。评估肾动脉阻力和搏动指数、肾小管损伤评分、肾小球面积和肾脏抗氧化能力。
在新生肾发生期间暴露于 HO 的啮齿动物的肾脏 Klotho 表达减少，肾小球增大，肾小管损伤评分升高。外源性 Klotho 给药可改善肾脏灌注，表现为阻力和搏动指数降低，抗氧化酶表达增加。
HO 暴露在新生肾发生期间可导致肾脏 Klotho 表达下降、肾脏灌注减少、肾小球增大和肾小管损伤。Klotho 的外源性给药减轻了 HO 引起的肾脏损伤并增强了抗氧化能力。
