Oxidant mechanisms in neonatal hypoxia-ischemia
Oxidant mechanisms in neonatal hypoxia-ischemia
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DOI：
10.1159/000046143
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发表时间：
2001-05-01
影响因子：
2.9
通讯作者：
Ferriero, DM
中科院分区：
文献类型：
--
作者：
Ferriero, DM
新生儿的大脑似乎是选择性地容易受到氧化应激。与活性氧代谢改变相关的几种潜在机制可以解释易感性增加。它们包括过氧化氢积累增加，随后出现神经毒性。H2O2积累引起的神经毒性增强可能与未成熟神经系统的清除能力不足有关，如谷胱甘肽过氧化物酶活性较低。促进清除酶的不成熟是发育中的神经系统无法维持谷胱甘肽储存。未成熟的神经系统富含铁，并且比成熟的神经系统具有更多的游离铁。由于H2O2由于这些不适当的防御机制而积累，它暴露于这种游离铁。这种暴露导致OH自由基（芬顿反应）的产生，OH自由基是一种更有效的自由基，可导致严重损害。在游离铁的情况下，H2O2快速转化为OH，使未成熟的神经系统产生增加的细胞毒性。了解氧化应激的分子机制将有助于更好地治疗新生儿缺氧缺血。版权所有（C）2001 S. Karger AG，巴塞尔。
The neonatal brain appears to be selectively vulnerable to oxidative stress. Several potential mechanisms associated with altered reactive oxygen species metabolism would explain the increased susceptibility. They include increased accumulation of hydrogen peroxide with subsequent neurotoxicity. This enhanced neurotoxicity from H2O2 accumulation may be related to inadequate scavenging abilities of the immature nervous system, such as lower glutathione peroxidase activity. Contributing to the immaturity of the scavenging enzymes is the inability of the developing nervous system to maintain glutathione stores. The immature nervous system is rich in iron, and has more free iron than the mature nervous system. As H2O2 accumulates because of these improper defense mechanisms, it is exposed to this free iron. This exposure results in the generation of OH radical (Fenton reaction), a more potent free radical that can cause severe damage. The rapid conversion of H2O2 to OH in the setting of free iron sets up the immature nervous system for increased cytotoxicity. Understanding the molecular mechanisms of oxidative stress will lead to better therapies for neonatal hypoxia-ischemia. Copyright (C) 2001 S. Karger AG, Basel.