Department of Gynecology, Jiangsu Province Hospital (The First Affiliated Hospital of Nanjing Medical University), 300 Guangzhou Road, Nanjing, 210000, China.
Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital (The Affiliated Hospital of Nanjing University Medical School), Nanjing, China.
Reprod Sci. 2021 Jan;28(1):186-196. doi: 10.1007/s43032-020-00280-w. Epub 2020 Aug 7.
Intrauterine growth restriction (IUGR) is, in general, accompanied by a reduction of the nephron number, which increases the risk of hypertension and renal dysfunction. Studies have revealed that ouabain can partially restore the number of nephrons during IUGR. However, there is limited information regarding the melioration of nephric structure and function. We used maternal malnutrition to induce an IUGR model in rats. Subsequently, we used a mini-pump to administer ouabain to IUGR rats during pregnancy. Male offspring were divided randomly into two groups. One group was fed a normal diet, whereas the other was fed an isocaloric 8% high-salt diet. Maternal malnutrition led to a reduction in the birth weight and number of nephrons in offspring. At the end of a 40-week follow-up period, offspring from the IUGR group had high blood pressure and abnormal excretion of urinary protein; these parameters were exacerbated in offspring fed a high-salt diet. However, ouabain administration during pregnancy could partially restore the number of nephrons in IUGR offspring, normalize blood pressure, and reduce urinary protein excretion, even when challenged with a high-salt diet. Pathology findings revealed that IUGR, particularly following feeding of a high-salt diet, damaged the ultrastructure of glomeruli, but these harmful effects were ameliorated in offspring treated with ouabain. Collectively, our data suggest that ouabain could rescue nephrogenesis in IUGR newborns and protect (at least in part) the structure and function of the kidney during adulthood even when encountering unfavorable environmental challenges in subsequent life.
宫内发育迟缓 (IUGR) 通常伴随着肾单位数量的减少，这增加了高血压和肾功能障碍的风险。研究表明，哇巴因可以部分恢复 IUGR 期间的肾单位数量。然而，关于肾脏结构和功能改善的信息有限。我们使用母体营养不良来诱导大鼠的 IUGR 模型。随后，我们使用微型泵在妊娠期间向 IUGR 大鼠给予哇巴因。雄性后代随机分为两组。一组喂食正常饮食，另一组喂食等热量的 8%高盐饮食。母体营养不良导致后代出生体重和肾单位数量减少。在 40 周的随访期结束时，IUGR 组的后代血压升高，尿蛋白排泄异常；这些参数在喂食高盐饮食的后代中更为严重。然而，妊娠期间给予哇巴因可以部分恢复 IUGR 后代的肾单位数量，使血压正常化，并减少尿蛋白排泄，即使在高盐饮食的挑战下也是如此。病理学发现表明，IUGR，特别是在喂食高盐饮食后，损害了肾小球的超微结构，但在接受哇巴因治疗的后代中，这些有害影响得到了改善。总的来说，我们的数据表明，哇巴因可以挽救 IUGR 新生儿的肾发生，并在成年期保护（至少部分保护）肾脏的结构和功能，即使在以后的生活中遇到不利的环境挑战。
