Makrakis John, Zimanyi Monika A, Black M Jane
Department of Anatomy & Cell Biology, Monash University, Post Office Box 13C, Melbourne, VIC 3800, Australia.
Pediatr Nephrol. 2007 Nov;22(11):1861-7. doi: 10.1007/s00467-007-0572-5. Epub 2007 Sep 12.
A reduced nephron complement at birth renders the kidney susceptible to renal disease in adulthood. Retinoic acid (RA; the active metabolite of vitamin A) is linked to nephrogenesis in vitro and in vivo. The aim of this study was to determine the effect of administration of retinoic acid in midgestation in rats on nephron endowment in offspring exposed to maternal protein restriction. Rats were fed either a normal-protein diet (NPD) or a low-protein diet (LPD) during pregnancy and lactation. Half of the dams in the LPD group were injected intraperitoneally with retinoic acid (20 mg/kg) during gestation at embryonic day 11.5. At 4 weeks of age, the offspring were anesthetized and perfusion-fixed, and nephron number estimated using unbiased stereological techniques. Body weight and kidney volume was significantly reduced in all LPD offspring. There was a significant 29% reduction in nephron number in the LPD group compared with the NPD offspring, whereas the number of nephrons in kidneys from the LPD + RA offspring was not significantly different compared with controls. In conclusion, administration of a single bolus dose of retinoic acid during midgestation restored nephron endowment to normal in offspring exposed to maternal protein restriction.
出生时肾单位数量减少会使肾脏在成年后易患肾脏疾病。视黄酸（RA；维生素A的活性代谢产物）在体外和体内均与肾发生有关。本研究的目的是确定在妊娠中期给大鼠施用视黄酸对暴露于母体蛋白质限制的后代肾单位数量的影响。在怀孕和哺乳期间，给大鼠喂食正常蛋白质饮食（NPD）或低蛋白质饮食（LPD）。LPD组中一半的母鼠在妊娠第11.5天胚胎期经腹腔注射视黄酸（20mg/kg）。在4周龄时，将后代麻醉并进行灌注固定，使用无偏倚的体视学技术估计肾单位数量。所有LPD后代的体重和肾脏体积均显著降低。与NPD后代相比，LPD组的肾单位数量显著减少29%，而LPD+RA后代肾脏中的肾单位数量与对照组相比无显著差异。总之，在妊娠中期单次推注视黄酸可使暴露于母体蛋白质限制的后代肾单位数量恢复正常。
