Ozone-induced alterations in glutathione in lung subcompartments of rats and monkeys
Ozone-induced alterations in glutathione in lung subcompartments of rats and monkeys
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DOI：
10.1165/ajrcmb.14.1.8534488
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发表时间：
1996-01-01
影响因子：
6.4
通讯作者：
Plopper, CG
中科院分区：
文献类型：
--
作者：
Duan, XZ;Buckpitt, AR;Plopper, CG
目前的研究旨在检验两个假设：(1)稳态还原型谷胱甘肽水平的差异是导致急性臭氧损伤易感性不同的原因；(2)还原谷胱甘肽浓度的升高解释了反复臭氧暴露造成的进一步伤害的耐受性。在大鼠和猴子的肺的明确的亚室中测量了谷胱甘肽，以比较不同物种(老鼠比猴子对臭氧不敏感)在肺的靶区(远端气管和终末细支气管区)和非靶区(叶支气管区、大支气管区、小支气管区和实质区)发生的变化。0.4ppm臭氧作用2 h后，大鼠气管内谷胱甘肽含量降低，1ppm臭氧作用2 h后，大鼠肺叶、细支气管处的谷胱甘肽浓度升高。在猴子中，大多数小室的谷胱甘肽水平在0.4或1.0ppm的臭氧暴露2小时内都没有改变，但主要的子舱(0.4ppm暴露时为对照的200%)和远端细支气管室(1ppm暴露时为对照的55%)例外。暴露90天(6小时/天×5天/周)的大鼠仅在1ppm的暴露水平下，远端细支气管处的谷胱甘肽(164%)升高。同样，暴露90天至1ppm O-3的猕猴远端细支气管处的谷胱甘肽水平是相应对照组的165%。这些结果表明：肺部靶区和非靶区以及敏感和不敏感物种中的谷胱甘肽水平不是观察到臭氧毒性差异的主要决定因素；肺小室对短期臭氧暴露的反应因呼吸道小室和物种而异；谷胱甘肽水平升高可能是长期暴露于O-3的大鼠和猴子的一些呼吸道上皮细胞适应的原因之一；使用明确的肺段提供了一种评估肺目标区域的变化而不稀释非目标区域的手段。
The current studies were designed to test two hypotheses: (1) differences in steady-state reduced glutathione levels are responsible for subcompartment differences in susceptibility to acute ozone injury, and (2) elevation of reduced glutathione concentrations accounts for the tolerance to further injury produced by repeated ozone exposure. Glutathione was measured in well-defined subcompartments of the lung of both rats and monkeys to compare alterations occurring in both target (distal trachea and terminal bronchiole) and nontarget areas (lobar bronchus, major daughter, minor daughter bronchus, and parenchyma) of the lung in species that differ in sensitivity to ozone exposure (rat is less susceptible than monkey). Glutathione concentrations were decreased in trachea of rats exposed to 0.4 ppm ozone for 2 h and increased in lobar bronchus and distal bronchiole after 2 h exposure at 1 ppm. In monkey, glutathione levels in most subcompartments were not altered by either 0.4 or 1.0 ppm ozone exposure for 2 h. The exceptions were the major daughter subcompartment (200% of control at 0.4 ppm exposure) and the distal bronchiole (55% of control at 1 ppm exposure). Ninety day ozone exposures (6 h/day x 5 days/week) in rats produced an elevation in glutathione (164% of control value) only in distal bronchiole at the 1 ppm exposure level. In a similar manner, glutathione levels in the distal bronchiole of monkeys exposed for 90 days to 1 ppm O-3 were 165% of the corresponding control values. These results suggest the following: glutathione levels in target and nontarget areas of the lung and in susceptible versus less susceptible species are not the primary determinant in the differences observed in ozone toxicity; the response of lung subcompartments to short-term ozone exposure varied depending on airway subcompartment and species; increased glutathione levels may be one reason for adaptation of some airway epithelial cells from rats and monkeys exposed to O-3 for long periods; and use of well-defined segments of the lung provides a means of assessing changes in target areas of the lung without dilution from nontarget areas.