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

尽管胎儿在分娩过程中经历了严重的缺氧和缺血，但胎儿的大脑受到未知机制的保护，免受缺氧缺血性损伤。在之前的一项研究中，我们发现，在脐带阻断后，足月大鼠胎儿的脑干PO2出现了矛盾的上升，而脑干血流却明显减少。本实验旨在探讨足月胎儿脑干PO2矛盾上升的机制。对这一现象有两种可能的解释：脑干PO2的矛盾上升是由于1)脑干中氧气的重新生成或2)氧气从血液以外的储存库释放。为了探讨可能性1)，我们进行了几项实验，包括a)超氧化物歧化酶（SOD）抑制剂对脑干PO2矛盾升高的影响，b)免疫印迹法定量分析胎儿脑SOD， c)脐带阻断后胎儿脑干一氧化氮（NO）的实时测量。在这些实验中，研究了缺氧缺血性损伤过程中产生的氧自由基产生O2的可能性。然而，我们没有发现任何证据支持这种可能性。为了研究可能性2，我们寻找了能与O2结合的化学物质。研究发现，成年大鼠的大脑中不存在这种物质，但胎儿的大脑仍有待于进一步的实验研究。虽然我们也对胎儿大脑血管与缺氧的关系进行了形态学研究，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。

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.