Koyama S, Kobayashi T, Kubo K, Sekiguchi M, Ueda G
Department of Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
Am Rev Respir Dis. 1992 Jun;145(6):1404-9. doi: 10.1164/ajrccm/145.6.1404.
Oxygen radicals have been implicated in the pathogenesis of acute lung injury associated with clinical and experimental sepsis. With the use of endotoxin infusion as an in vivo model of sepsis we studied the effect of recombinant-human superoxide dismutase (r-hSOD; 4,200 U/mg), an enzyme that catalyzes the dismutation of superoxide anion, on both the physiologic and biochemical lung changes in awake sheep. Sheep (n = 11) were prepared for chronic measurement of pulmonary hemodynamics and lung fluid balance. Paired experiments were performed in seven of the animals in which they received either endotoxin (1 microgram/kg) alone or in combination with r-hSOD in random order. An additional four sheep received r-hSOD without the lipopolysaccharide. Intravenous infusion of r-hSOD (a loading dose of 12,600 U/kg followed by a maintenance dose of 14,700 U/kg/h for 7 h) resulted in substantial SOD activity, measured by electron spin resonance spectrometry, both in plasma and in lung lymph, and attenuated the expected changes in pulmonary arterial pressure and lung lymph flow after administration of endotoxin. When administered without endotoxin, r-hSOD produced no perceptible change in pulmonary hemodynamics and lung fluid balance. These data suggest that superoxide anion plays an important role in endotoxin-induced lung injury in sheep.
氧自由基与临床和实验性脓毒症相关的急性肺损伤发病机制有关。我们以内毒素输注作为脓毒症的体内模型，研究了重组人超氧化物歧化酶（r-hSOD；4200 U/mg），一种催化超氧阴离子歧化反应的酶，对清醒绵羊肺的生理和生化变化的影响。绵羊（n = 11）被准备用于长期测量肺血流动力学和肺液体平衡。在七只动物中进行配对实验，它们随机接受单独的内毒素（1微克/千克）或与r-hSOD联合使用。另外四只绵羊接受了不含脂多糖的r-hSOD。静脉输注r-hSOD（负荷剂量为12600 U/kg，随后维持剂量为14700 U/kg/h，持续7小时）导致通过电子自旋共振光谱法测量的血浆和肺淋巴液中SOD活性显著升高，并减轻了内毒素给药后肺动脉压和肺淋巴液流量的预期变化。当在无内毒素的情况下给药时，r-hSOD对肺血流动力学和肺液体平衡没有产生明显变化。这些数据表明超氧阴离子在绵羊内毒素诱导的肺损伤中起重要作用。
