Boubred Farid, Daniel Laurent, Buffat Christophe, Feuerstein Jean-Marc, Tsimaratos Michel, Oliver Charles, Dignat-George Françoise, Lelièvre-Pégorier Martine, Simeoni Umberto
INSERM UMR608, Faculté de Pharmacie, Université de la Méditerranée, Marseille, France.
Am J Physiol Renal Physiol. 2009 Oct;297(4):F943-51. doi: 10.1152/ajprenal.90704.2008. Epub 2009 Aug 5.
Low birth weight is associated with an increased risk of hypertension and renal dysfunction at adulthood. Such an association has been shown to involve a reduction of nephron endowment and to be enhanced by accelerated postnatal growth in humans. However, while low-birth-weight infants often undergo catch-up growth, little is known about the long-term vascular and renal effects of accelerated postnatal growth. We surimposed early postnatal overfeeding (OF; reduction of litter size during the suckling period) to appropriate-birth-weight (NBW+OF) and intrauterine growth restriction (IUGR; IUGR+OF) pups, obtained after a maternal gestational low-protein diet. Blood pressure (systolic blood pressure; SBP) and renal function (glomerular filtration rate; GFR) were measured in young and aging offspring. Glomerulosclerosis and nephron number were determined in aging offspring (22 mo). Nephron number was reduced in both IUGR and IUGR+OF male offspring (by 24 and 26%). GFR was reduced by 40% in 12-mo-old IUGR+OF male offspring, and both NBW+OF and IUGR+OF aging male offspring had sustained hypertension (+25 mmHg) and glomerulosclerosis, while SBP and renal function were unaffected in IUGR aging offspring. Female offspring were unaffected. In conclusion, in this experimental model, early postnatal OF in the neonatal period has major long-lasting effects. Such effects are gender dependent. Reduced nephron number alone, associated with IUGR, may not be sufficient to induce long-lasting physiological alterations, and early postnatal OF acts as a "second hit." Early postnatal OF is a suitable model with which to study the long-term effects of postnatal growth in the pathogenesis of vascular disorders and renal disease.
低出生体重与成年后患高血压和肾功能不全的风险增加相关。这种关联已被证明与肾单位数量减少有关，并且在人类中会因出生后生长加速而增强。然而，虽然低出生体重婴儿经常经历追赶生长，但对于出生后生长加速对血管和肾脏的长期影响知之甚少。我们对通过母体孕期低蛋白饮食获得的正常出生体重（NBW+OF）和宫内生长受限（IUGR；IUGR+OF）幼崽在出生后早期进行过度喂养（OF；哺乳期减少窝仔数）。在幼年和老年后代中测量血压（收缩压；SBP）和肾功能（肾小球滤过率；GFR）。在老年后代（22个月）中测定肾小球硬化和肾单位数量。IUGR和IUGR+OF雄性后代的肾单位数量均减少（分别减少24%和26%）。12个月大的IUGR+OF雄性后代的GFR降低了40%，NBW+OF和IUGR+OF老年雄性后代均患有持续性高血压（+25 mmHg）和肾小球硬化，而IUGR老年后代的SBP和肾功能未受影响。雌性后代未受影响。总之，在这个实验模型中，新生儿期出生后早期OF具有重大的长期影响。这些影响具有性别依赖性。仅与IUGR相关的肾单位数量减少可能不足以引起长期的生理改变，出生后早期OF起到“二次打击”的作用。出生后早期OF是研究出生后生长在血管疾病和肾脏疾病发病机制中的长期影响的合适模型。
