Canada A T, Herman L A, Young S L
Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Am J Physiol. 1995 Apr;268(4 Pt 1):L539-45. doi: 10.1152/ajplung.1995.268.4.L539.
The role of animal age in the lethal response to > 98% oxygen has been extensively studied, with the observation that neonatal rats were resistant while mature animals were sensitive. Antioxidant enzymes increased during the oxygen exposure in neonatal but not in mature rats, suggesting they were important in the age-related toxicity difference. Because no studies had compared the response of mature and old rats to hyperoxia, we exposed Fischer 344 rats, aged 2 and 27 mo, to > 98% oxygen. Unexpectedly, the old rats lived significantly longer than young, 114 and 65 h, respectively. No histopathological differences were found to explain the results. Of the antioxidants, only glutathione peroxidase (GPx) activity was higher in the lungs of nonexposed old rats. Superoxide dismutase (SOD) was higher in the young, results opposite those expected if SOD was important in the lethality difference. No antioxidant induction occurred in the old oxygen-exposed rats. These results suggest that although there may be a role for GPx, mechanisms in addition to antioxidant protection and inflammation are likely responsible for the age-related difference in hyperoxia lethality.
动物年龄在对>98%氧气的致死反应中的作用已得到广泛研究，观察发现新生大鼠具有抗性，而成年动物则敏感。在新生大鼠而非成年大鼠的氧气暴露期间，抗氧化酶增加，这表明它们在与年龄相关的毒性差异中很重要。由于没有研究比较过成年和老年大鼠对高氧的反应，我们将2月龄和27月龄的Fischer 344大鼠暴露于>98%的氧气中。出乎意料的是，老年大鼠的存活时间明显长于年轻大鼠，分别为114小时和65小时。未发现组织病理学差异来解释这些结果。在抗氧化剂中，只有谷胱甘肽过氧化物酶（GPx）活性在未暴露的老年大鼠肺中较高。超氧化物歧化酶（SOD）在年轻大鼠中较高，这一结果与如果SOD在致死率差异中起重要作用时预期的结果相反。老年氧气暴露大鼠未发生抗氧化剂诱导。这些结果表明，尽管GPx可能起作用，但除了抗氧化保护和炎症之外的机制可能是高氧致死率与年龄相关差异的原因。
