Tryka A F, Godleski J J, Skornik W A, Brain J D
Exp Lung Res. 1983 Nov;5(3):155-71. doi: 10.3109/01902148309061511.
The concomitant treatment of hamsters with bleomycin and hyperoxia results in a synergistic development of pulmonary injury. We exposed hamsters for 72 hr to 70% oxygen following a single intratracheal instillation of bleomycin (0.16 U/100 g body weight). Groups of 10 animals were killed at 3, 6, 10, 30, 60, 90, and 120 days after instillation for histopathologic and morphometric assessment. Diffuse alveolar damage developed acutely. At 30 days, the intense acute cellular infiltrate had subsided, leaving a focal interstitial pneumonitis. Morphometric quantitation at 10 days revealed that 33.5 +/- 5.3% (x +/- SE) of the lung was diseased; there was apparent healing by 30 days, when 10.5 +/- 2.0% of the lung was diseased. However, progression to diffuse pneumonitis with fibrosis was seen at 60, 90, and 120 days, when 30.2 +/- 4.9%, 38.5 +/- 5.8%, and 38.8 +/- 4.5% of the lung was diseased, respectively. In vivo pulmonary function studies on treated animals at 25 and 55 days showed decreasing dynamic compliance and increased minute ventilation, which corroborates the presence of interstitial fibrosis. We conclude that simultaneous treatment of hamsters with bleomycin and hyperoxia results in interstitial fibrosis with a distribution and progression that mimics human pulmonary fibrosis. This model appears ideally suited for the study of progressive fibrosis and will be useful when development of a widely distributed lesion is crucial.
对仓鼠同时使用博来霉素和高氧会导致肺部损伤协同发展。在单次气管内滴注博来霉素（0.16 U/100 g体重）后，将仓鼠暴露于70%氧气环境中72小时。每组10只动物在滴注后第3、6、10、30、60、90和120天处死，进行组织病理学和形态计量学评估。急性弥漫性肺泡损伤出现。在30天时，强烈的急性细胞浸润消退，留下局灶性间质性肺炎。10天时的形态计量学定量显示，33.5±5.3%（x±SE）的肺组织患病；到30天时明显愈合，此时10.5±2.0%的肺组织患病。然而，在60、90和120天时出现进展为伴有纤维化的弥漫性肺炎，此时分别有30.2±4.9%、38.5±5.8%和38.8±4.5%的肺组织患病。对治疗动物在25天和55天时进行的体内肺功能研究显示动态顺应性降低，分钟通气量增加，这证实了间质性纤维化的存在。我们得出结论，对仓鼠同时使用博来霉素和高氧会导致间质性纤维化，其分布和进展类似于人类肺纤维化。该模型似乎非常适合研究进行性纤维化，当广泛分布病变的发展至关重要时将很有用。
