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Prevention of developmental disorders of intra-uterine growth retarded infants with growth factors.

使用生长因子预防子宫内生长迟缓婴儿的发育障碍。

基本信息

批准号：
14571048
负责人：
TAKESHIMA Yasuhiro
金额：
$ 2.05万
依托单位：
Kobe University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571048/
关键词：
IUGR Insulin-like growth factor IGF-1 MBP PLP MBP PLP 子宮内発育遅延 IU GR insulin-like growth factor myelin basic protein proteolipid protein

项目摘要

The aim of this study is to determine the effect of undernutrition-induced intra-uterine growth retardation (IUGR) on the development of myelination and to clarify the role of insulin-like growth factor (IGF)-1 in the developing brain.Combination of the starvation of dams between embryonic day 17〜20 and restriction of feeding time of pups between birth〜postnatal day (P) 7 caused severe IUGR, resulting significantly lighter body weight up to P20. In this IUGR model, we investigated the expression levels of myelin-forming proteins, myelin basic protein (MBP) and proteolipid protein (PLP), using western blot analyses. MBP levels decreased to 58% in cerebral cortex and to 41% in cerebellum on P12, however they recovered to control level on P15. In striatum there was no decrease in MBP level. On the other hand, the expression levels of PLP did not decrease but increased to more than 200% of control group. PLP is more primitive in view of differentiation than MBP, which may result in their different expressions in IUGR brain.Intra-ventricular administration of IGF-1 on P7 accelerated the increase of MBP on P12. 5μg of IGF-1 was enough to recover MBP level in cerebral cortex and 10μg was necessary in cerebellum. On P15 any accelerating effect of IGF-1 on the expression of MBP and PLP was not observed.In conclusion IUGR causes insufficient forming of myelin sheath in cerebrum and cerebellum, which may lead to neurological sequelae in IUGR infants. IGF-1 may have a key role in achieving appropriate myelin formation in under-nutritional condition.

为探讨营养不良引起的宫内生长迟缓（IUGR）对髓鞘形成的影响及胰岛素样生长因子-1（IGF-1）在脑发育中的作用，在胚胎17 ~ 20天饥饿母鼠和出生~出生后7天限制幼仔喂养时间的联合作用下，造成严重IUGR，导致显著更轻的体重直到P20。在这个IUGR模型中，我们研究了髓鞘形成蛋白，髓鞘碱性蛋白（MBP）和蛋白脂质蛋白（PLP）的表达水平，使用蛋白质印迹分析。在P12时，大脑皮质和小脑的MBP水平分别下降至58%和41%，但在P15时恢复至对照水平。在纹状体中，MBP水平没有降低。另一方面，PLP的表达水平没有降低，而是增加到对照组的200%以上。PLP在分化上较MBP更为原始，这可能是导致二者在IUGR脑内表达差异的原因之一，P7脑室内注射IGF-1可促进P12 MBP的升高。5μg IGF-1足以恢复大脑皮层MBP水平，小脑需要10μg。结论：IUGR患儿大脑和小脑髓鞘形成不足，可能导致IUGR患儿神经系统后遗症。IGF-1可能在营养不良条件下实现适当的髓鞘形成中起关键作用。