正在进行的肾脏形成过程中新生儿肾元丢失后长期肾纤维化的性别差异。

IF 2.4 Q1 PEDIATRICS
Carlos Menendez-Castro, Nada Cordasic, Fabian B Fahlbusch, Joachim Woelfle, Karl F Hilgers, Andrea Hartner
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引用次数: 0

摘要

背景:临床研究表明,女性在肾脏疾病的发生和发展中起保护作用。最近的实验研究表明,在正在进行的肾脏形成过程中,雄性大鼠早期肾元丢失伴随着严重的长期后遗症。在人类中,肾元的形成主要发生在妊娠晚期,在妊娠36周时停止。由于围产期并发症,早产婴儿在这一脆弱时期分娩可能发生急性肾元损失。大鼠肾形成持续到出生后第10天,反映了人类早产儿肾形成持续的情况。在我们的新生儿不切除肾动物模型中,雌性和雄性大鼠在出生第1天不切除肾。假设性别依赖性差异,1年后评估长期肾脏预后。结果:在两性中,新生儿肾切除术后在1岁时没有出现动脉高血压。未切除肾的雌性和雄性动物均出现代偿性体重增加和剩余肾脏的肾小球肥大。间质炎症和纤维化的选定标记物受性别依赖性调节。新生儿肾切除术后,雌性小鼠单核细胞趋化蛋白-1表达增加,而雄性小鼠肾小管间质M1巨噬细胞浸润明显增加。通过半定量评分和desmin染色来评估,未切除肾脏的新生雄性大鼠比雌性大鼠有更多的肾小球硬化和足细胞损伤。RT-PCR结果显示,雌性大鼠新生期单肾切除后对侧剩余肾脏wt-1、nephrin、synaptopodin、gdnf、itga8等肾脏发育和功能的候选基因表达高于雄性大鼠。结论:基于这些观察,我们得出结论,女性对活动性肾形成下急性肾单位损失的肾脏长期反应具有保护作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Sex differences in long-term kidney fibrosis following neonatal nephron loss during ongoing nephrogenesis.

Sex differences in long-term kidney fibrosis following neonatal nephron loss during ongoing nephrogenesis.

Sex differences in long-term kidney fibrosis following neonatal nephron loss during ongoing nephrogenesis.

Sex differences in long-term kidney fibrosis following neonatal nephron loss during ongoing nephrogenesis.

Background: Clinical studies suggest that female sex plays a protective role in the development and progression of kidney disease. Recent experimental studies indicate that in male rats early nephron loss under ongoing nephrogenesis is accompanied by severe long-term sequelae. In humans, nephron formation occurs mainly in the third trimester, ceasing with 36 weeks of gestation. Due to perinatal complications, preterm infants delivered during this vulnerable period may undergo acute nephron loss. In rats nephrogenesis persists until postnatal day 10, reflecting the situation of human preterms with persisting nephrogenesis. In our animal model of neonatal uninephrectomy, female and male rats were uninephrectomized at day 1 of life. Hypothesizing sex-dependent differences, long-term renal outcome was assessed after 1 year.

Results: In both sexes, neonatal uninephrectomy was not followed by arterial hypertension at 1 year of age. Compensatory weight gain and glomerular hypertrophy of the remaining kidney occurred in uninephrectomized female and male animals. Selected markers of interstitial inflammation and fibrosis were regulated sex-dependently. The expression of monocyte chemoattractant protein-1 was increased in females, while tubulointerstitial infiltration by M1 macrophages was significantly higher in males after neonatal uninephrectomy. Neonatally uninephrectomized male rats had more glomerulosclerosis and podocyte damage compared to females, which was assessed by a semiquantitative score and desmin staining. RT-PCR revealed that after neonatal uninephrectomy in the remaining contralateral kidney of female rats the expression of candidate genes of renal development and function, i.e., wt-1, nephrin, synaptopodin, gdnf, and itga8 was higher than in males.

Conclusions: Based on these observations we conclude that female sex is protective in the long-term response of the kidney to acute nephron loss under active nephrogenesis.

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