Eremia Simona C, de Boo Hendrina A, Bloomfield Frank H, Oliver Mark H, Harding Jane E
Liggins Institute, University of Auckland, 1142 Auckland, New Zealand.
Endocrinology. 2007 Jun;148(6):2963-72. doi: 10.1210/en.2006-1701. Epub 2007 Mar 8.
To date, there is no known prenatal treatment for intrauterine growth restriction (IUGR). IGF-I is an important regulator of fetal growth and circulating IGF-I concentrations are reduced in IUGR fetuses. We investigated whether any of three different methods of fetal IGF-I administration would reverse IUGR in sheep. Animals were randomized into five groups: control (n = 17), IUGR + saline (SAL, n = 17), IUGR + iv IGF-I (IGF-IV, n = 14), IUGR + intraamniotic IGF-I (IGF-AF, n = 14), or IUGR + intraamniotic IGF-I with nutrients (IGF-NUT, n = 16). Weekly IGF-I dose was 360 microg in each treatment group. IUGR was induced by placental embolization between 93 and 99 d and treatment was from 100-128 d gestation (term = 147 d). Embolization caused asymmetrical IUGR with reduced fetal growth rates and body and organ weights, but increased brain to liver weight ratio, at post mortem. Embolized fetuses were also hypoxemic and hypoglycemic and had reduced circulating IGF-I and insulin concentrations. IGF-AF and IGF-IV significantly increased fetal growth rates, but only IGF-AF significantly increased fetal liver weight, compared with saline-treated fetuses. Fetal weights and brain to liver weight ratios in all IGF-I-treated fetuses were intermediate between the control and SAL groups. Addition of nutrients reduced the effects of amniotic IGF-I treatment and increased fetal hemoglobin and lactate concentrations. Treatments did not change fetal plasma IGF-I and insulin concentrations. This is the first report of an intrauterine treatment significantly increasing fetal growth rate in established IUGR. Amniotic IGF-I administration may provide the basis for a clinically applicable prenatal treatment for the IUGR fetus.
迄今为止，尚无已知的针对宫内生长受限（IUGR）的产前治疗方法。胰岛素样生长因子-I（IGF-I）是胎儿生长的重要调节因子，IUGR胎儿的循环IGF-I浓度降低。我们研究了三种不同的胎儿IGF-I给药方法是否能逆转绵羊的IUGR。将动物随机分为五组：对照组（n = 17）、IUGR + 生理盐水（SAL，n = 17）、IUGR + 静脉注射IGF-I（IGF-IV，n = 14）、IUGR + 羊膜内注射IGF-I（IGF-AF，n = 14）或IUGR + 羊膜内注射IGF-I并添加营养物质（IGF-NUT，n = 16）。每个治疗组的每周IGF-I剂量为360微克。在妊娠93至99天通过胎盘栓塞诱导IUGR，并在妊娠100 - 128天（足月为147天）进行治疗。栓塞导致不对称性IUGR，胎儿生长速率、体重和器官重量降低，但死后脑肝重量比增加。栓塞胎儿还存在低氧血症和低血糖，循环IGF-I和胰岛素浓度降低。与生理盐水处理的胎儿相比，IGF-AF和IGF-IV显著提高了胎儿生长速率，但只有IGF-AF显著增加了胎儿肝脏重量。所有接受IGF-I治疗的胎儿的体重和脑肝重量比介于对照组和SAL组之间。添加营养物质降低了羊膜内IGF-I治疗的效果，并增加了胎儿血红蛋白和乳酸浓度。治疗未改变胎儿血浆IGF-I和胰岛素浓度。这是关于宫内治疗显著提高已确诊IUGR胎儿生长速率的首篇报道。羊膜内注射IGF-I可能为IUGR胎儿的临床适用产前治疗提供基础。
