Last J A, Gelzleichter T R, Pinkerton K E, Walker R M, Witschi H
Department of Internal Medicine, School of Medicine, University of California, Davis 95616-8542.
Am Rev Respir Dis. 1993 Aug;148(2):487-94. doi: 10.1164/ajrccm/148.2.487.
Sprague-Dawley rats were exposed for 6 h daily to 0.8 ppm of ozone and 14.4 ppm of nitrogen dioxide. Approximately 7 to 10 wk after the initiation of exposure, animals began to demonstrate respiratory insufficiency and severe weight loss. About half of the rats died between Days 55 and 78 of exposure; no overt ill effects were observed in animals exposed to filtered air, to ozone alone, or to nitrogen dioxide. Biochemical findings in animals exposed to ozone and nitrogen dioxide included increased lung content of DNA, protein, collagen, and elastin, which was about 300% higher than the control values. The collagen-specific crosslink hydroxy-pyridinium, a biomarker for mature collagen in the lung, was decreased by about 40%. These results are consistent with extensive breakdown and remodeling of the lung parenchyma and its associated vasculature. Histopathologic evaluation showed severe fibrosis, alveolar collapse, honeycombing, macrophage and mast cell accumulation, vascular smooth muscle hypertrophy, and other indications of severe progressive interstitial pulmonary fibrosis and end-stage lung disease. This unique animal model of progressive pulmonary fibrosis resembles the final stages of human idiopathic pulmonary fibrosis and should facilitate studying underlying mechanisms and potential therapy of progressive pulmonary fibrosis.
将Sprague-Dawley大鼠每天暴露于0.8 ppm的臭氧和14.4 ppm的二氧化氮中6小时。在开始暴露后约7至10周，动物开始出现呼吸功能不全和严重体重减轻。约一半的大鼠在暴露的第55天至78天之间死亡；在暴露于过滤空气、仅臭氧或仅二氧化氮的动物中未观察到明显的不良影响。暴露于臭氧和二氧化氮的动物的生化结果包括肺中DNA、蛋白质、胶原蛋白和弹性蛋白含量增加，比对照值高约300%。肺中成熟胶原蛋白的生物标志物——胶原蛋白特异性交联羟基吡啶鎓减少了约40%。这些结果与肺实质及其相关脉管系统的广泛破坏和重塑一致。组织病理学评估显示严重纤维化、肺泡塌陷、蜂窝状改变、巨噬细胞和肥大细胞积聚、血管平滑肌肥大以及严重进行性间质性肺纤维化和终末期肺病的其他迹象。这种独特的进行性肺纤维化动物模型类似于人类特发性肺纤维化的终末期，应有助于研究进行性肺纤维化的潜在机制和治疗方法。
