Schreuder Michiel F, Nyengaard Jens R, Fodor Mariann, van Wijk Joanna A E, Delemarre-van de Waal Henriette A
Department of Pediatrics, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands.
J Am Soc Nephrol. 2005 Oct;16(10):2913-9. doi: 10.1681/ASN.2004100875. Epub 2005 Aug 10.
A link exists between low birth weight and diseases in adulthood, such as hypertension, cardiovascular disease, and insulin resistance. Intrauterine growth restriction (IUGR) has been used to explain this association and has been shown to lead to a nephron endowment in humans. A reduction in glomerular number has been described in animal models with induced low birth weight as well but not in animals with spontaneous low birth weight. It therefore is debatable whether the models are suitable. The effect on glomerular number and size was studied in rats with naturally occurring IUGR and experimental IUGR, induced by bilateral uterine artery ligation. Design-based stereologic methods were used. Urinary protein excretion was determined as a measure of renal damage. Results showed a decrease of approximately 20% in glomerular number in both groups of IUGR (control 35,400, naturally occurring IUGR 30,900, and experimental IUGR 28,000 glomeruli per kidney). Mean glomerular volume was increased in both IUGR groups, which was associated with an increased proteinuria. It is concluded that IUGR leads to a nephron endowment with a compensatory glomerular enlargement. This compensation is associated with more proteinuria in the long run. Uterine artery ligation in the pregnant rat is a suitable model to study the effects of IUGR on the kidney.
低出生体重与成年期疾病之间存在联系，如高血压、心血管疾病和胰岛素抵抗。宫内生长受限（IUGR）已被用于解释这种关联，并且已证明其会导致人类肾单位数量减少。在诱导低出生体重的动物模型中也描述了肾小球数量的减少，但在自然发生低出生体重的动物中未观察到。因此，这些模型是否合适存在争议。我们研究了自然发生IUGR的大鼠以及由双侧子宫动脉结扎诱导的实验性IUGR大鼠的肾小球数量和大小的变化。采用基于设计的体视学方法。测定尿蛋白排泄量以衡量肾脏损伤程度。结果显示，两组IUGR大鼠的肾小球数量均减少了约20%（对照组每肾35,400个肾小球，自然发生IUGR组为30,900个，实验性IUGR组为28,000个）。两组IUGR大鼠的平均肾小球体积均增加，且与蛋白尿增加有关。研究得出结论，IUGR会导致肾单位数量减少并伴有肾小球代偿性增大。从长远来看，这种代偿与更多的蛋白尿有关。妊娠大鼠子宫动脉结扎是研究IUGR对肾脏影响的合适模型。
