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在宫内生长受限兔模型中使用重组人胰岛素样生长因子-1进行胎儿治疗。

Fetal therapy with rhIGF-1 in a rabbit model of intrauterine growth retardation.

作者信息

Skarsgard E D, Amii L A, Dimmitt R A, Sakamoto G, Brindle M E, Moss R L

机构信息

Department of Surgery, Lucile Packard Children's Hospital, Palo Alto, California 94025, USA.

出版信息

J Surg Res. 2001 Jul;99(1):142-6. doi: 10.1006/jsre.2001.6120.

Abstract

BACKGROUND

Intrauterine growth retardation (IUGR) may, in part, be due to a deficiency of insulin-like growth factor-1 (IGF-1). The objectives of this study were to determine the relationship between fetal serum IGF-1 levels and fetal and placental size in a rabbit model of IUGR and to compare two techniques of selective, exogenous IGF-1 administration (transamniotic and branch uterine arterial catheter infusion) to growth-retarded fetuses in utero.

MATERIALS AND METHODS

Pregnant rabbits (n = 6) had their fetuses harvested near term (31 days) for fetal and placental weighing and serum collection. Growth-retarded fetuses were selectively infused for 7 days with recombinant human IGF-1 (rhIGF-1; 1,440 ng/day) either through a transamniotic catheter (n = 8) or via an adjacent uterine arterial branch catheter (n = 6). Opposite horn runts were sham catheterized, but not infused. At term, the fetal runt pairs and their placentas were harvested and weighed, and their serum was collected. The correlation between fetal and placental weight and endogenous serum IGF-1 was calculated (Pearson coefficient, r), while paired t-tests were used to compare the means between the IGF-1-infused and control groups.

RESULTS

There was a significant correlation between fetal (r = 0.4230; P = 0.022) and placental weight (r = 0.4166; P = 0.025) and endogenous serum levels of IGF-1. Transamniotic infusion of rhIGF-1 was associated with an increase in serum IGF-1 level (254 +/- 79 vs 351 +/- 101 ng/ml, P = 0.04) and placental weight (5.4 +/- 2.3 vs 7.1 +/- 3.2 g, P = 0.005), and with a trend toward increased fetal weight between matched fetal runt pairs. Fetal mortality in the uterine arterial catheterized group was 76%, and there was no significant difference in fetal or placental weight or IGF-1 levels between infused and noninfused survivors.

CONCLUSIONS

Endogenous fetal serum levels correlate with fetal and placental size in the rabbit IUGR model. Transamniotic administration of rhIGF-1 significantly increases serum IGF-1 levels and placental weight of fetal runts, while uterine vessel catheterization results in prohibitive fetal mortality and does not increase fetal or placental growth or IGF-1 levels.

摘要

背景

宫内生长受限(IUGR)可能部分归因于胰岛素样生长因子-1(IGF-1)缺乏。本研究的目的是确定IUGR兔模型中胎儿血清IGF-1水平与胎儿及胎盘大小之间的关系,并比较两种向宫内生长受限胎儿选择性给予外源性IGF-1的技术(经羊膜腔和子宫动脉分支导管灌注)。

材料与方法

怀孕母兔(n = 6)在接近足月(31天)时剖宫取胎,进行胎儿和胎盘称重及血清采集。对生长受限胎儿通过经羊膜腔导管(n = 8)或经相邻子宫动脉分支导管(n = 6)选择性输注重组人IGF-1(rhIGF-1;1440 ng/天)7天。对侧子宫角的发育迟缓胎儿进行假导管插入但不进行输注。足月时,收集发育迟缓胎儿及其胎盘并称重,采集血清。计算胎儿和胎盘重量与内源性血清IGF-1之间的相关性(Pearson系数,r),采用配对t检验比较IGF-1输注组和对照组之间的均值。

结果

胎儿(r = 0.4230;P = 0.022)及胎盘重量(r = 0.4166;P = 0.025)与内源性血清IGF-1水平之间存在显著相关性。经羊膜腔输注rhIGF-1可使血清IGF-1水平升高(254±79 vs 351±101 ng/ml,P = 0.04)及胎盘重量增加(5.4±2.3 vs 7.1±3.2 g,P = 0.005);在配对的发育迟缓胎儿之间,胎儿体重有增加趋势。子宫动脉导管插入组胎儿死亡率为76%,输注组和未输注组存活胎儿的胎儿或胎盘重量及IGF-1水平无显著差异。

结论

在兔IUGR模型中,内源性胎儿血清水平与胎儿及胎盘大小相关。经羊膜腔给予rhIGF-1可显著提高发育迟缓胎儿的血清IGF-1水平和胎盘重量,而子宫血管导管插入导致胎儿死亡率过高,且未增加胎儿或胎盘生长及IGF-1水平。

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