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Studies on the protective mechanism of the fetal brain against hypoxic-ischemic insult during delivery

胎儿大脑对分娩过程中缺氧缺血损伤的保护机制研究

基本信息

批准号：
15390507
负责人：
NAKAMURA Shoji
金额：
$ 8.13万
依托单位：
Yamaguchi University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

项目摘要

Although the fetuses experiences severe hypoxia and ischemia during delivery, the fetal brain is protected from hypoxic-ischemic insults by unknown mechanism. In a previous study, we found that at-term rat fetuses revealed a paradoxical rise in brainstem PO2 following umbilical cord occlusion, while brainstem blood flow was markedly reduced. The present experiments were designed to investigate the mechanism of this paradoxical rise in brainstem PO2 of at-term fetuses. There are two possible explanations for this phenomenon : The paradoxical rise in brainstem PO2 is due to 1) de novo generation of O2 in the brainstem or 2)O2 release from a reservoir other than blood.To investigate possibility 1), we performed several experiments, including a) the effects of a superoxide dismutase (SOD) inhibitor on the paradoxical rise in brainstem PO2, b) Quantitative analysis of fetal brain SOD by immunoblot and c) Real-time measurement of nitrogen monoxide (NO) in the fetal brainstem following umbilical cord occlusion. In these experiments, the possibility was examined that O2 is produced from oxygen radicals which generate during hypoxic-ischemic insults. However, we did not find any evidence supporting this possibility. To investigate possibility 2), we searched chemical substances which can bind to O2. It was found that there was no such a substance in the adult rat brain, but the fetal brain remains to be investigated in future experiments. Although we also performed a morphological study on blood vessels in the fetal brain in relation to hypoxia, no significant change was found between control and hypoxia groups.In summary, we could not reach a conclusion on the paradoxical rise in brainstem PO2 of at-term fetuses, although a variety of experiments were performed.

虽然胎儿在分娩过程中经历了严重的缺氧和缺血，但其脑保护机制尚不清楚。在之前的一项研究中，我们发现足月胎鼠在脐带闭塞后脑干PO2出现矛盾的上升，而脑干血流量显著减少。本实验旨在研究足月胎儿脑干PO2反常升高的机制。对于这种现象有两种可能的解释：脑干PO2的反常升高是由于1)脑干中O2的从头产生或2)O2从血液以外的储存库中释放。为了研究这种可能性，我们进行了几个实验，包括a)超氧化物歧化酶(SOD)抑制剂对脑干PO2反常升高的影响，b)免疫印迹法定量分析胎儿脑内SOD，以及c)实时测量脐带闭塞后胎儿脑干中一氧化氮(NO)的含量。在这些实验中，研究了氧气是由缺氧缺血期间产生的氧自由基产生的可能性。然而，我们没有发现任何支持这种可能性的证据。为了研究这种可能性，我们寻找了能与O2结合的化学物质。研究发现，成年大鼠的大脑中没有这种物质，但胎鼠的大脑还有待于未来的实验研究。虽然我们也进行了与缺氧有关的胎儿脑血管的形态学研究，但在对照组和缺氧组之间没有发现明显的变化。综上所述，尽管进行了各种实验，但我们无法得出足月胎儿脑干PO2矛盾上升的结论。