缺氧对儿童胰岛素样生长因子-I（IGF-I）、胰岛素样生长因子-II（IGF-II）、胰岛素样生长因子结合蛋白-3（IGFBP-3）、酸性不稳定亚基（ALS）和胰岛素样生长因子结合蛋白-1（IGFBP-1）调节以及对IGF1R基因表达的影响。
Impact of hypoxia on IGF-I, IGF-II, IGFBP-3, ALS and IGFBP-1 regulation and on IGF1R gene expression in children.
作者信息
Custodio Rodrigo José, do Carmo Custodio Viviane Imaculada, Scrideli Carlos Alberto, Sader Milani Soraya Lopes, Cervi Maria Célia, Cupo Palmira, Martinelli Carlos Eduardo
机构信息
Department of Paediatrics, School of Medicine of Ribeirão Preto, University of São Paulo, University Hospital, Brazil.
出版信息
Growth Horm IGF Res. 2012 Oct;22(5):186-91. doi: 10.1016/j.ghir.2012.07.001. Epub 2012 Aug 14.
UNLABELLED
Hypoxia is one of many factors involved in the regulation of the IGF system. However, no information is available regarding the regulation of the IGF system by acute hypoxia in humans.
OBJECTIVE
The aim of this study was to evaluate the effect of acute hypoxia on the IGF system of children.
DESIGN
Twenty-seven previously health children (14 boys and 13 girls) aged 15 days to 9.5 years were studied in two different situations: during a hypoxemic state (HS) due to acute respiratory distress and after full recovery to a normoxemic state (NS). In these two situations oxygen saturation was assessed with a pulse-oximeter and blood samples were collected for serum IGF-I, IGF-II, IGFBP-1, IGFBP-3, ALS and insulin determination by ELISA; fluoroimmunometric assay determination for GH and also for IGF1R gene expression analysis in peripheral lymphocytes by quantitative real-time PCR. Data were paired and analyzed by the Wilcoxon non-parametric test.
RESULTS
Oxygen saturation was significantly lower during HS than in NS (P<0.0001). IGF-I and IGF-II levels were lower during HS than in NS (P<0.0001 and P=0.0004, respectively). IGFBP-3 levels were also lower in HS than in NS (P=0.0002) while ALS and basal GH levels were higher during HS (P=0.0015 and P=0.014, respectively). Moreover, IGFBP-1 levels were higher during HS than in NS (P=0.004). No difference was found regarding insulin levels. The expression of IGF1R mRNA as 2(-ΔΔCT) was higher during HS than in NS (P=0.03).
CONCLUSION
The above results confirm a role of hypoxia in the regulation of the IGF system also in humans. This effect could be direct on the liver and/or mediated by GH and it is not restricted to the hepatocytes but involves other cell lines. During acute hypoxia a combination of alterations usually associated with reduced IGF action was observed. The higher expression of IGF1R mRNA may reflect an up-regulation of the transcriptional process.
未标注
缺氧是参与胰岛素样生长因子（IGF）系统调节的众多因素之一。然而，关于急性缺氧对人类IGF系统的调节作用尚无相关信息。
目的
本研究旨在评估急性缺氧对儿童IGF系统的影响。
设计
对27名年龄在15天至9.5岁的健康儿童（14名男孩和13名女孩）在两种不同情况下进行研究：急性呼吸窘迫导致的低氧血症状态（HS）期间以及完全恢复到正常氧血症状态（NS）后。在这两种情况下，使用脉搏血氧仪评估血氧饱和度，并采集血样，通过酶联免疫吸附测定法（ELISA）测定血清IGF-I、IGF-II、IGFBP-1、IGFBP-3、酸性不稳定亚基（ALS）和胰岛素；采用荧光免疫测定法测定生长激素（GH），并通过定量实时聚合酶链反应（PCR）分析外周淋巴细胞中IGF1R基因的表达。数据进行配对，并采用Wilcoxon非参数检验进行分析。
结果
HS期间的血氧饱和度显著低于NS期间（P<0.0001）。HS期间的IGF-I和IGF-II水平低于NS期间（分别为P<0.0001和P=0.0004）。HS期间的IGFBP-3水平也低于NS期间（P=0.0002），而HS期间的ALS和基础GH水平较高（分别为P=0.0015和P=0.014）。此外，HS期间的IGFBP-1水平高于NS期间（P=0.004）。胰岛素水平未发现差异。HS期间IGF1R mRNA的表达以2(-ΔΔCT)表示高于NS期间（P=0.03）。
结论
上述结果证实了缺氧在人类IGF系统调节中的作用。这种作用可能直接作用于肝脏和/或由GH介导，且不仅限于肝细胞，还涉及其他细胞系。在急性缺氧期间，观察到通常与IGF作用降低相关的多种改变组合。IGF1R mRNA的较高表达可能反映了转录过程的上调。
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