Department of Pediatrics, University of California, San Francisco, CA 94143-1346, USA.
Semin Fetal Neonatal Med. 2010 Aug;15(4):196-202. doi: 10.1016/j.siny.2010.05.006. Epub 2010 Jul 4.
Oxygen is essential for multicellular existence. Its reduction to water by the mitochondrial electron transport chain forms the cornerstone of aerobic metabolism. Conditions in which oxygen is limiting for electron transport result in bioenergetic collapse in metazoans. However, compared with postnatal existence, all of mammalian development occurs in a hypoxic environment in utero. Not just an epiphenomenon, this 'physiological hypoxia' is required for the activation of a transcriptional response mediated by the hypoxia-inducible factor (HIF) family of transcriptional regulators that coordinates the expression of hundreds of genes, many with developmentally critical functions. Oxygen tension, therefore, is a morphogen. Understanding the physiological significance of hypoxia responses during human development and the role of the HIF family of transcriptional regulators will have important consequences for the care of preterm neonates. Defining clinical care guidelines for the proper oxygenation of critically ill neonates that take account of these observations is therefore of paramount importance. The pharmacological stabilization of HIF family members may therefore have clinical utility in premature infants in whom this important morphogen has been inactivated by exposure to supraphysiological oxygen levels.
氧气对于多细胞生物的存在至关重要。其通过线粒体电子传递链还原为水，形成有氧代谢的基石。在氧气对电子传递有限制的情况下，多细胞生物会发生生物能量崩溃。然而，与出生后相比，哺乳动物的所有发育过程都发生在子宫内的低氧环境中。这种“生理性缺氧”不仅是一种现象，它还需要缺氧诱导因子（HIF）转录调节因子家族来激活转录反应，协调数百个基因的表达，其中许多基因具有发育关键功能。因此，氧气张力是一种形态发生素。了解人类发育过程中缺氧反应的生理意义以及 HIF 转录调节因子家族的作用，对于早产儿的护理将具有重要意义。因此，定义适当氧合的临床护理指南，以考虑到这些观察结果，对于患有严重疾病的新生儿至关重要。在暴露于超生理氧水平而使这种重要形态发生素失活的早产儿中，HIF 家族成员的药理学稳定可能具有临床实用性。
