Chessex P, Lavoie J C, Laborie S, Vallée J
Research Center, Hôpital Ste-Justine, Department of Pediatrics, University of Montreal, Quebec, Canada.
Pediatr Res. 1999 Sep;46(3):305-10. doi: 10.1203/00006450-199909000-00009.
The imbalance between high oxidant loads and immature antioxidant defenses is associated with long-term complications of prematurity. Glutathione is a central element among the antioxidants. Depletion of pulmonary glutathione accelerates the development of oxygen-induced lung injury in neonatal animal models. After the observation that newborn infants exposed to oxygen have low glutathione levels, a study was designed to test the hypothesis that in neonates from a species susceptible to oxygen toxicity, the lethal effect of hyperoxia is related to a low availability of substrates for glutathione production rather than an impairment in synthetic activity. One-day-old guinea pigs, randomly assigned to room air or oxygen (>95%), were fed by their mothers (n = 16) or i.v. by dextrose (n = 14) or by total parenteral nutrition (TPN, n = 20). After 3 d, glutathione and activities of enzymes involved in maintaining intracellular glutathione levels were determined in lungs and liver. The lethal effect of oxygen (p < 0.05) observed in animals without TPN was not related to glutathione depletion, as oxygen induced a 33% increase in lung glutathione, positively correlated (r2 = 0.35) with enhanced synthesis. With TPN, the animals were protected against the lethal effects of hyperoxia and lung glutathione increased by 67% in oxygen. The results suggest that the glutathione demand by the lungs in the presence of an oxidant stimulus was met by the increased (p < 0.001) hepatic production supported by TPN. Under hyperoxic conditions, early nutritional support is of vital importance.
高氧化负荷与未成熟的抗氧化防御之间的失衡与早产的长期并发症有关。谷胱甘肽是抗氧化剂中的核心成分。在新生动物模型中，肺内谷胱甘肽的消耗会加速氧诱导的肺损伤的发展。在观察到暴露于氧气的新生儿谷胱甘肽水平较低后，设计了一项研究来检验以下假设：在对氧毒性敏感的物种的新生儿中，高氧的致死作用与谷胱甘肽生成底物的可用性低有关，而不是与合成活性受损有关。将1日龄豚鼠随机分为室内空气组或氧气组（>95%），分别由其母亲喂养（n = 16）、静脉输注葡萄糖（n = 14）或接受全胃肠外营养（TPN，n = 20）。3天后，测定肺和肝脏中的谷胱甘肽以及参与维持细胞内谷胱甘肽水平的酶的活性。在未接受TPN的动物中观察到的氧气致死作用（p < 0.05）与谷胱甘肽耗竭无关，因为氧气导致肺谷胱甘肽增加33%，与合成增强呈正相关（r2 = 0.35）。接受TPN的动物受到高氧致死作用的保护，氧气组肺谷胱甘肽增加67%。结果表明，在存在氧化刺激的情况下，肺对谷胱甘肽的需求通过TPN支持的肝脏产量增加（p < 0.001）得到满足。在高氧条件下，早期营养支持至关重要。
