Tryka A F, Witschi H, Lindenschmidt R C
Exp Mol Pathol. 1985 Dec;43(3):348-58. doi: 10.1016/0014-4800(85)90071-1.
The concomitant treatment of rats with bleomycin and hyperoxia results in synergistic development of pulmonary injury. We exposed rats to 70% oxygen for 72 hr following an intratracheal instillation of bleomycin (0.2 U/kg body wt). Animals were killed 15, 30, 60 and 90 days after treatment for hydroxyproline, cell kinetics, and histopathologic analysis. A 16% increase in hydroxyproline over controls was seen 15 days after treatment which was manifested by the proliferation phase of diffuse alveolar damage and an increase in cell labeling by tritiated thymidine. Thirty days after treatment the hydroxyproline remained elevated while lung injury appeared to be healing with a residual focal interstitial pneumonitis and a drop in cell labeling. Between 60 and 90 days, there was an additional significant increase in hydroxyproline to 44% over controls. Diffuse interstitial pneumonitis with fibrosis was observed. Cell labeling remained constant between 60 and 90 days. We conclude that the treatment of rats with bleomycin and hyperoxia results in slowly progressive pulmonary fibrosis. The increase in hydroxyproline in the chronic phase was not accompanied by an increase in cell proliferation, and therefore may have resulted from an increase in cellular production of hydroxyproline rather than increased number of cells producing collagen.
用博来霉素和高氧同时处理大鼠会导致肺损伤协同发展。在气管内注入博来霉素（0.2 U/kg体重）后，将大鼠暴露于70%氧气中72小时。在处理后15、30、60和90天处死动物，进行羟脯氨酸、细胞动力学和组织病理学分析。处理后15天，羟脯氨酸比对照组增加16%，表现为弥漫性肺泡损伤的增殖期和氚标记胸腺嘧啶核苷细胞标记增加。处理后30天，羟脯氨酸仍保持升高，而肺损伤似乎正在愈合，伴有残留的局灶性间质性肺炎和细胞标记下降。在60至90天之间，羟脯氨酸比对照组又显著增加至44%。观察到伴有纤维化的弥漫性间质性肺炎。在60至90天之间细胞标记保持恒定。我们得出结论，用博来霉素和高氧处理大鼠会导致缓慢进展的肺纤维化。慢性期羟脯氨酸的增加并未伴有细胞增殖的增加，因此可能是由于细胞羟脯氨酸产生增加而非产生胶原蛋白的细胞数量增加所致。
