组织氧张力和大脑对缺氧的敏感性

Maria Erecińska, Ian A. Silver
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引用次数: 577

摘要

哺乳动物的大脑是一个高度氧化的器官,虽然它只占总体重的一小部分,但却占了身体氧气消耗的不成比例的大比例(人类分别约为2%和20%)。然而,大脑中的分压和氧气浓度很低,而且不均匀。有大量的酶使用O2作为底物,其中最重要的是细胞色素c氧化酶,它是线粒体ATP产生的关键。细胞色素c氧化酶对氧的亲和力非常高,在正常条件下确保氧化磷酸化活性不降低,直至极低的PO2。相比之下,许多其他相关酶的氧Km值在环境脑气张力内或以上,因此它们的作用非常依赖于生理范围内的氧水平。在其多种多样的功能中,氧分压和浓度控制活性氧的产生、基因的表达和离子通道的功能。大脑的氧气供应限制在“临界”水平以下,并最终阻止氧化磷酸化,急剧减少细胞(ATP)并导致离子梯度崩溃。神经元活动停止,如果不能迅速重新引入氧气,细胞就会死亡。这篇综述的目的是简要讨论哺乳动物大脑的中心氧依赖过程和缺氧的短期后果,但不包括长期适应慢性缺氧的机制。特别强调最近引起关注和/或争议的问题。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Tissue oxygen tension and brain sensitivity to hypoxia

Mammalian brain is a highly oxidative organ and although it constitutes only a small fraction of total body weight it accounts for a disproportionately large percentage of bodily oxygen consumption (in humans about 2 and 20%, respectively). Yet, the partial pressure and concentration of oxygen in the brain are low and non-uniform. There is a large number of enzymes that use O2 as a substrate, the most important of which is cytochrome c oxidase, the key to mitochondrial ATP production. The affinity of cytochrome c oxidase for oxygen is very high, which under normal conditions ensures undiminished activity of oxidative phosphorylation down to very low PO2. By contrast, many other relevant enzymes have Km values for oxygen within, or above, the ambient cerebral gas tension, thus making their operations very dependent on oxygen level in the physiological range. Among its multiple, versatile functions, oxygen partial pressure and concentration control production of reactive oxygen species, expression of genes and functions of ion channels. Limitation of oxygen supply to the brain below a ‘critical’ level reduces, and eventually blocks oxidative phosphorylation, drastically decreases cellular (ATP) and leads to a collapse of ion gradients. Neuronal activity ceases and if oxygen is not re-introduced quickly, cells die. The object of this review is to discuss briefly the central oxygen-dependent processes in mammalian brain and the short-term consequences of O2 deprivation, but not the mechanisms of long-term adaptation to chronic hypoxia. Particular emphasis is placed on issues which have been the focus of recent attention and/or controversy.

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