Azid 에 의한 Mouse 폐내 산소독성의 증강

Abstract

고농도 산소에 노출시 폐손상의 병인론 중 주된 요소로 reactive oxygen species가 관계되고 있음은 이미 잘 알려져 있는 사실이다. Azide는 superoxide radicals와 hydrogen peroxide를 제거해서 산속독성 방어기전에 중요한 역할을 하는 superoxide dismutase(SOD)와 catalase의 억제제로 알려져 있다. 그러므로 azide의 처치로 산소독성을 증가시킬 수 있을 것으로 가정하였다. Mouse를 azide(8.1 ㎎/㎏ body weight)로 전처치한 것과 하지 않은 것으로 나누어 100% O₂에 노출시킨 후 폐에서 산소독성의 생화학적 지표가 되는 효소와 oxygen radical을 측정하였다. Oxygen radical의 생성량은 azide와 100% O₂로 처치한 실험군에서 증가하여 superoxide radical는 24시간에, hydroxyl radical은 48시간에 최고를 나타내었다. Xanthine oxidase는 시간 경과에 따라 활성도가 감소했으며, 처치 후 6시간에는 Type O의 비율이 90% 이상 이었다. Azide와 100% O₂로 처치한 실험군에서 Mn-SOD와 glutathione peroxide는 다른 실험군 보다 활성이 유의하게 높았던 반면, catalase는 활성이 유의하게 낮았다. 생존 시간은 azide와 100% O₂로 처치한 실험군이 다른 모든 실험군보다 유의하게 감소했다. Liposomal SOD(1,500 units/mouse)를 복강내로 투여했을 때 생존시간은 유의하게 연장되었다. 이와같은 결과는, 100% O₂에 노출된 mouse 폐에서 reactive oxygen species의 과생산에 의해 산소독성이 발생할 수 있고, azide에 의해 reactive oxygen species 제거 효소가 억제되면 산소독성이 증강되며, liposomal SOD는 산소독성으로부터 mouse를 보호하여 생존시간을 연장시킬 수 있음을 나타낸 것이라 하겠다.

An increased production of reactive oxygen species has been postulated to be a major factor in the pathogenesis of lung damage during hyperoxia. Azide is an inhibitor of superoxide dismutase (SOD) and catalase. These enzymes are important in defence mechanism against oxygen toxicity by removing superoxide radicals and hydrogen peroxide. Therefore, azide treatment could enhance oxygen toxicity. Mice were exposed to 100% O₂ (1 atm) with or without pretreatment with azide (8.1 ㎎/㎏ body weight). Biochemical indicators of oxygen toxicity in the lung of mouse were measured. Production of superoxide radicals and hydroxyl radicals increased in the lung of mouse treated with azide and 100% O₂. Superoxide radical generation was maximized at 24 h after the treatment, while the highest hydroxyl radical production occurred at 48 h. Xanthine oxidase activity was continuously decreased by the treatment with azide and 100% O₂. During the first 6 h of the treatment ~90% of xanthine oxidase activity appeared as the type $quot;O$quot;. The Mn-SOD and glutathione peroxidase in azide and 100% O₂ treated group showed a significantly higher activity than those in the azide or 100% O₂ treated groups, while catalase activity was significantly lower in the azide/O₂-treated group. Survival time in azide and 100% O₂exposed group was significantly shorter than that in the azide or 100% O₂ treated groups. When SOD-containing liposomes (1,500 units/mouse) were introduced into the peritoneal cavity, the survival time was significantly extended. These results suggested that oxygen toxicity occurred in the lung of 100% O₂ exposed mouse by overproduction of reactive oxygen species and that the toxicity was exacerbated by azide-induced inhibition of enzymes in capable of removing reactive oxygen species. Liposomal SOD protected the mouse from the oxygen toxicity and extended the survival time.