Prolonged hypoxia induced by the reduction of maternal uterine blood flow alters insulin-like growth factor-binding protein-1 (IGFBP-1) and IGFBP-2 gene expression in the ovine fetus.
Prolonged hypoxia induced by the reduction of maternal uterine blood flow alters insulin-like growth factor-binding protein-1 (IGFBP-1) and IGFBP-2 gene expression in the ovine fetus.
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母体子宫血流量减少引起的长期缺氧会改变绵羊胎儿中胰岛素样生长因子结合蛋白-1 (IGFBP-1) 和 IGFBP-2 基因的表达。
DOI：
10.1210/endo.131.4.1382958
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发表时间：
1992
期刊：
影响因子：
4.8
通讯作者：
V. Han
中科院分区：
文献类型：
--
作者：
K. McLellan;S. Hooper;A. Bocking;P. Delhanty;I. Phillips;D. J. Hill;V. Han
胰岛素样生长因子(IGF-I和IGF-II)是一种由多种胎儿组织合成的促有丝分裂和分化的多肽。在循环和组织液中，IGFS与结合蛋白(Bps)结合，这些结合蛋白不仅可以作为载体蛋白发挥作用，还可以抑制或调节IGFS的生物学作用。我们之前已经证明，母体子宫血流量减少24小时导致绵羊胎儿长期缺氧会导致选定的胎儿组织DNA合成率下降。为了确定这种效应是由于组织IGFS及其结合蛋白局部合成的改变，还是由于IGFS和IGFBPs系统浓度的变化，我们研究了编码IGFS和IGFBPs的mRNAs在选定组织中的丰度以及血浆IGFS和IGFBPs的变化。通过降低母体子宫血流量(RUBF)，对妊娠115~120天的绵羊胎儿(n=6)进行24 h低氧。对照组(n=6)在没有RUBF的情况下接受相同的手术。分别于实验前、实验中、实验结束后连续采集血浆标本，24 h末采集组织标本，发现缺氧胎儿血浆IGF-I、IGF-II平均浓度在缺氧过程中均低于对照组，但差异无统计学意义。缺氧24小时后，对照组和缺氧组胎儿肺、肌肉、胸腺和肾脏组织中IGF-I和IGF-II的表达水平相似。低氧组胎儿肝脏IGF-I和IGF-II的相对丰度较低，但只有IGF-I的mRNA水平与对照组有显著差异(P<；0.05)。与对照组相比，缺氧组胎儿肝脏中IGFBP-1mRNA水平升高3~7倍，部分缺氧组(2/6)肾脏中有IGFBP-1mRNA表达。此外，低氧胎儿肝脏(50%)和肾脏(30%)的IGFBP-2mRNA水平降低。肝脏IGFBP-1mRNA丰度增加，肝脏和肾脏IGFBP-2mRNA丰度降低，胎儿血浆IGFBP-1水平升高，IGFBP-2水平降低。IGFBP-3的血浆水平和组织信使核糖核酸丰度均未见变化。对血浆IGFBP-1和IGFBP-2变化的时程分析表明，IGFBP-1和IGFBP-2的变化发生在缺氧4h内。
Insulin-like growth factors (IGF-I and IGF-II) are potent mitogenic and differentiating peptides which are synthesized by many fetal tissues. In the circulation and tissue fluids, IGFs are bound to binding proteins (BPs) which not only function as carrier proteins, but also inhibit or modulate the biological actions of IGFs. We have previously shown that prolonged hypoxia in the ovine fetus induced by the reduction of maternal uterine blood flow for 24 h causes a reduction in the DNA synthesis rate in selected fetal tissues. To determine if this effect is due to alterations in the local synthesis of tissue IGFs and their binding proteins or to changes in systemic concentrations of IGFs and IGFBPs, we have investigated the abundance of mRNAs encoding IGFs and IGFBPs in selected tissues and changes in plasma IGFs and IGFBPs. Ovine fetuses (115-120 days gestation; n = 6) underwent 24 h of hypoxia by the reduction of maternal uterine blood flow (RUBF). Controls (n = 6) underwent the same surgical procedure without RUBF. Serial plasma samples were collected before, during, and after the experiment, and tissues were collected at the end of 24 h. Mean plasma IGF-I and IGF-II concentrations tended to be lower in hypoxic fetuses than in controls during the course of hypoxia, but these differences were not statistically significant. Tissue mRNA levels for IGF-I and IGF-II in lung, muscle, thymus, and kidney were similar in control and hypoxic fetuses after 24 h of hypoxia. The relative abundance of liver IGF-I and IGF-II mRNAs was lower in hypoxic fetuses, but only IGF-I mRNA levels were significantly different from the control values (P < 0.05). Compared to control fetuses, IGFBP-1 mRNA levels in the liver of hypoxic fetuses were increased 3- to 7-fold, and IGFBP-1 mRNA expression was induced in kidneys of some hypoxic fetuses (two of six). In addition, IGFBP-2 mRNA levels were decreased in the liver (50%) and kidney (30%) of hypoxic fetuses. The increase in liver IGFBP-1 mRNA abundance and the decrease in liver and kidney IGFBP-2 mRNA abundance were accompanied by an increase in IGFBP-1 levels and a decrease in IGFBP-2 levels in fetal plasma. No changes were observed in either plasma levels or tissue mRNA abundance for IGFBP-3. Analysis of the time course of changes in plasma revealed that the changes in IGFBP-1 and IGFBP-2 occurred within 4 h of hypoxia.(ABSTRACT TRUNCATED AT 400 WORDS)
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影响因子：
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