Smith L J, Anderson J
Department of Medicine (Pulmonary Division), Northwestern University Medical School, Chicago, IL 60611.
Am Rev Respir Dis. 1992 Dec;146(6):1452-7. doi: 10.1164/ajrccm/146.6.1452.
Several reports suggest there is a relationship between lung glutathione (GSH) levels and susceptibility to oxygen-induced lung damage. However, studies of other organs and cells indicate that a better relationship may exist between mitochondrial GSH levels and oxidant damage. We determined whether there is a similar relationship in the lung using a well-characterized mouse model and a series of interventions that alter lung GSH levels and susceptibility to oxygen-induced lung damage. Mice were fasted or given buthionine sulfoximine (BSO, 20 mM), which reduce total lung GSH levels and increase susceptibility to oxygen-induced lung damage. Mice were also given glutathione monoethyl ester (GSH-ME) intraperitoneally (5 or 10 mM/kg/day for 2 days) or intratracheally (0.2 mM once) in an attempt to increase lung GSH levels. Fasting for up to 3 days and the administration of BSO for 7 to 10 days decreased total lung GSH levels (p < 0.001 for both) but not lung mitochondrial GSH levels. Intraperitoneal administration of GSH-ME increased mitochondrial GSH levels (p < 0.001 in both fed and fasted mice), but it had little effect on total lung GSH levels and no effect on susceptibility to oxygen-induced lung damage. Exposure to 100% oxygen increased mitochondrial GSH levels in both the fed and fasted mice to nearly the same extent (p < 0.001 for both). However, the fasted mice had lower total lung GSH levels compared with the fed mice (p < 0.05) and increased susceptibility to 100% oxygen.(ABSTRACT TRUNCATED AT 250 WORDS)
多项报告表明，肺组织中谷胱甘肽（GSH）水平与对氧诱导性肺损伤的易感性之间存在关联。然而，对其他器官和细胞的研究表明，线粒体GSH水平与氧化损伤之间可能存在更密切的关系。我们使用特征明确的小鼠模型以及一系列改变肺组织GSH水平和对氧诱导性肺损伤易感性的干预措施，来确定肺组织中是否存在类似的关系。小鼠被禁食或给予丁硫氨酸亚砜胺（BSO，20 mM），这会降低肺组织总GSH水平并增加对氧诱导性肺损伤的易感性。还对小鼠腹腔注射谷胱甘肽单乙酯（GSH-ME，5或10 mM/kg/天，共2天）或气管内注射（0.2 mM，一次），试图提高肺组织GSH水平。禁食长达3天以及给予BSO 7至10天会降低肺组织总GSH水平（两者均p < 0.001），但不会降低肺线粒体GSH水平。腹腔注射GSH-ME可增加线粒体GSH水平（喂食和禁食小鼠均p < 0.001），但对肺组织总GSH水平影响不大，对氧诱导性肺损伤的易感性也无影响。暴露于100%氧气中，喂食和禁食小鼠的线粒体GSH水平升高幅度几乎相同（两者均p < 0.001）。然而，与喂食小鼠相比，禁食小鼠的肺组织总GSH水平较低（p < 0.05），对100%氧气的易感性增加。（摘要截断于250字）
