Buonocore G, Perrone S, Bracci R
Institute of Preventive Pediatrics and Neonatology, University of Siena, Italy.
Biol Neonate. 2001;79(3-4):180-6. doi: 10.1159/000047088.
Newborns and particularly preterm infants are at high risk of oxidative stress and they are very susceptible to free radical oxidative damage. Indeed, there is evidence of an imbalance between antioxidant- and oxidant-generating systems which causes oxidative damage. The brain may be especially at risk of free radical-mediated injury because neuronal membranes are rich in polyunsaturated fatty acids and because the human newborn has a relative deficiency of brain superoxide dismutase and glutathione peroxidase. The brain of the term fetus is at higher risk of oxidative stress than that of the preterm fetus, as a consequence of its higher concentration of polyunsaturated fatty acids and the maturity of the N-methyl-D-aspartate receptor system at term. There seems to be a maturation-dependent window of vulnerability to free radical attack during oligodendrocyte development. Early in its differentiation, the oligodendrocyte may be vulnerable because of active acquisition of iron for differentiation at a time of relative delay in the development of certain key antioxidant defenses in the brain. Excess free iron and deficient iron-binding and -metabolizing capacity are additional features favoring oxidant stress in premature infants. Free radicals may be generated by different mechanisms, such as ischemia-reperfusion, neutrophil and macrophage activation, Fenton chemistry, endothelial cell xanthine oxidase, free fatty acid and prostaglandin metabolism and hypoxia. Reactive oxidant production by these different mechanisms contributes in a piecewise manner to the pathogenesis of perinatal brain injury.
新生儿尤其是早产儿面临氧化应激的高风险，并且极易受到自由基氧化损伤。事实上，有证据表明抗氧化剂生成系统和氧化剂生成系统之间存在失衡，这会导致氧化损伤。大脑可能特别容易受到自由基介导的损伤，因为神经元膜富含多不饱和脂肪酸，而且人类新生儿的脑超氧化物歧化酶和谷胱甘肽过氧化物酶相对缺乏。足月儿的大脑比早产儿的大脑面临更高的氧化应激风险，这是由于其多不饱和脂肪酸浓度较高以及足月时N-甲基-D-天冬氨酸受体系统成熟。在少突胶质细胞发育过程中，似乎存在一个依赖成熟度的自由基攻击易损窗口。在其分化早期，少突胶质细胞可能很脆弱，因为在大脑某些关键抗氧化防御发育相对延迟的时候，它为了分化而积极摄取铁。过量的游离铁以及铁结合和代谢能力不足是早产儿氧化应激的其他促成因素。自由基可通过不同机制产生，如缺血再灌注、中性粒细胞和巨噬细胞激活、芬顿化学反应、内皮细胞黄嘌呤氧化酶、游离脂肪酸和前列腺素代谢以及缺氧。这些不同机制产生的活性氧化剂以分段方式促成围产期脑损伤的发病机制。
