Thakur A, Sase M, Lee J J, Thakur V, Buchmiller T L
Division of Pediatric Surgery, Harbor-UCLA Medical Center, Torrance, California 90509, USA.
J Pediatr Surg. 2000 Jun;35(6):898-904; discussion 904-5. doi: 10.1053/jpsu.2000.6914.
BACKGROUND/PURPOSE: The maternal administration of steroids promotes fetal maturative effects in the gastrointestinal tract. To determine if fetal insulin-like growth factor-1 (IGF-1) expression is altered in response to maternal dexamethasone administration, this rabbit model of intrauterine growth retardation (IUGR) was utilized.
Eight pregnant rabbits received either dexamethasone (Dex 0.1 mg/kg/d intramuscular), or normal saline (Cont) on gestational days 26 and 27. Fetuses were harvested on gestational day 28 or 29 and were identified as favored (Fav) or runt (Runt): DexFav, DexRunt, ContFav, and ContRunt. Fetal weight was recorded and the serum, amniotic fluid, liver, kidney, and small intestine (SI) were collected. Reverse transcription polymerase chain reaction (RT-PCR) was used to measure IGF-1/beta-actin mRNA densitometric band ratios in all tissues. Radioimmunoassay (RIA) was used to measure IGF-1 protein levels in the serum and amniotic fluid.
Weight was decreased in the Runt fetuses at all time-points (P < .08). The percent weight accretion from day 28 to 29, was greatest in the DexRunt fetus (P < .001), suggesting "catch-up" growth. All Dex fetuses (Fav and Runt) had increased liver and proximal, middle and distal SI IGF-1 mRNA at day 28 and elevated levels in the liver, proximal and distal SI at day 29 compared with control fetuses. The DexRunt fetuses had serum IGF-1 protein surpassing that of the DexFav fetus at day 28.
This report provides the first description of maternal steroid administration effecting a marked increase in fetal IGF-1 mRNA expression and IGF-1 protein levels in an in vivo rabbit model of IUGR. The growth-retarded fetus appears to be particularly responsive.
背景/目的：母体使用类固醇可促进胎儿胃肠道的成熟效应。为了确定胎儿胰岛素样生长因子-1（IGF-1）的表达是否会因母体使用地塞米松而发生改变，本研究采用了兔宫内生长受限（IUGR）模型。
8只怀孕母兔在妊娠第26天和第27天分别接受地塞米松（0.1mg/kg/d肌肉注射）或生理盐水（对照）。在妊娠第28天或第29天收集胎儿，并分为优势胎儿（Fav）或发育迟缓胎儿（Runt）：地塞米松处理的优势胎儿（DexFav）、地塞米松处理的发育迟缓胎儿（DexRunt）、对照优势胎儿（ContFav）和对照发育迟缓胎儿（ContRunt）。记录胎儿体重，并收集血清、羊水、肝脏、肾脏和小肠（SI）。采用逆转录聚合酶链反应（RT-PCR）测量所有组织中IGF-1/β-肌动蛋白mRNA光密度带比值。采用放射免疫分析法（RIA）测量血清和羊水中IGF-1蛋白水平。
发育迟缓胎儿在所有时间点体重均下降（P<.08）。从第28天到第29天，地塞米松处理的发育迟缓胎儿体重增加百分比最大（P<.001），表明有“追赶”生长现象。与对照胎儿相比，所有地塞米松处理的胎儿（优势胎儿和发育迟缓胎儿）在第28天肝脏以及近端、中端和远端小肠的IGF-1 mRNA增加，在第29天肝脏、近端和远端小肠的水平升高。地塞米松处理的发育迟缓胎儿在第28天血清IGF-1蛋白超过地塞米松处理的优势胎儿。
本报告首次描述了在兔IUGR体内模型中，母体使用类固醇导致胎儿IGF-1 mRNA表达和IGF-1蛋白水平显著增加。生长受限胎儿似乎对此特别敏感。
