Department of Biochemistry, Memorial University of Newfoundland, St. John's, Nfld., Canada.
Neonatology. 2011;100(4):380-6. doi: 10.1159/000326341. Epub 2011 Jul 27.
Impaired fetal growth and rapid postnatal growth are associated with programming of hypertension and metabolic syndrome in adulthood.
This study evaluated this phenomenon in a novel spontaneous intrauterine growth-restricted (IUGR) model in Yucatan miniature pigs.
IUGR piglets (n = 6, 3 days old, 0.73 ± 0.11 kg) were paired with a normal weight (NW) same-sex littermate (n = 6, 1.11 ± 0.13 kg), fed milk replacer for 4 weeks followed by a standard diet ad libitum for 5 h/day. At 9 months of age, arterial blood pressure (BP) telemeters were implanted to assess BP before (0.5% NaCl) and after (4.5% NaCl) a 7-day salt-loading period. At 10 months of age, nephron numbers were determined.
Prior to sexual maturity, IUGR pigs showed greater (p < 0.05) relative feed intake and experienced significant catch-up growth. Adult IUGR pigs also had higher BP (diastolic BP: 93.8 ± 5.5 vs. 90.0 ± 8.7 mm Hg, p < 0.05) and 43% fewer nephrons per kidney (p < 0.05). Nephron number was positively associated with birth weight and negatively correlated with BP (p < 0.05). Acute salt loading increased BP in both groups (p < 0.05); however, the degree of salt sensitivity was similar between groups (p > 0.05).
In conclusion, IUGR piglets have reduced nephron endowment associated with a modest BP increase in early adulthood. This new model can be used to conduct longitudinal mechanistic studies on the early programming phenomenon.
胎儿生长受限和快速的生后生长与成年期高血压和代谢综合征的发生有关。
本研究旨在评估尤卡坦小型猪这一新型自发性宫内生长受限(IUGR)模型中的这一现象。
IUGR 仔猪(n = 6,3 日龄,0.73 ± 0.11 kg)与同性别正常体重(NW)的同窝仔猪配对(n = 6,1.11 ± 0.13 kg),用代乳喂养 4 周,然后自由采食标准饮食 5 h/d。在 9 月龄时,植入动脉血压(BP)遥测仪以评估盐负荷前(0.5% NaCl)和后(4.5% NaCl)7 天的 BP。在 10 月龄时,确定肾单位数量。
在性成熟前,IUGR 仔猪表现出更高的(p < 0.05)相对采食量,并经历了显著的追赶性生长。成年 IUGR 仔猪的 BP 也更高(舒张压:93.8 ± 5.5 与 90.0 ± 8.7 mm Hg,p < 0.05),每只肾脏的肾单位数量减少 43%(p < 0.05)。肾单位数量与出生体重呈正相关,与 BP 呈负相关(p < 0.05)。急性盐负荷增加了两组的 BP(p < 0.05);然而,两组间的盐敏感性程度相似(p > 0.05)。
总之,IUGR 仔猪的肾单位数量减少与成年早期血压适度升高有关。该新型模型可用于对早期编程现象进行纵向机制研究。