Coursin D B, Cihla H P
Department of Anesthesiology, University of Wisconsin Clinical Science Center, Madison 53792.
Toxicology. 1988 Dec 16;53(1):45-55. doi: 10.1016/0300-483x(88)90235-1.
Rats were treated with subcutaneous injections of either saline or 1, 3, or 5 units of bleomycin (BLM) each day for 5 days (5, 15, or 25 units total dose). One half of each group of animals was exposed to 80% oxygen for 4 days during BLM dosings. Rats treated with both 25 units BLM and hyperoxia died after being returned to room air. All remaining rats were sacrificed 6 weeks following the end of treatment. Of the BLM rats in room air, only the lungs of the 15-unit group exhibited histological change, a mild diffuse interstitial disease. Both lower dose groups demonstrated slight increases in hydroxy-proline (OHP) content, a marker of collagen deposition or lung injury. The lungs of BLM rats exposed to hyperoxia demonstrated greater increases in total lung OHP levels. The lungs of the 15-unit group demonstrated lesions consistent with diffuse interstitial pulmonary fibrosis. Short-term, sublethal hyperoxia clearly potentiated injury in the rat following subcutaneous BLM treatment as assessed by either lethality or markers of pulmonary pathology.
大鼠每天皮下注射生理盐水或1、3或5单位博来霉素（BLM），持续5天（总剂量分别为5、15或25单位）。每组动物的一半在注射BLM期间暴露于80%氧气环境中4天。接受25单位BLM和高氧处理的大鼠在恢复至室内空气后死亡。治疗结束6周后，处死所有剩余大鼠。在室内空气中的BLM处理大鼠中，只有15单位组的肺表现出组织学变化，即轻度弥漫性间质性疾病。两个较低剂量组的羟脯氨酸（OHP）含量均略有增加，OHP是胶原蛋白沉积或肺损伤的标志物。暴露于高氧环境的BLM处理大鼠的肺总OHP水平升高更为明显。15单位组的肺表现出与弥漫性间质性肺纤维化一致的病变。通过致死率或肺部病理学标志物评估，短期亚致死性高氧明显增强了皮下注射BLM后大鼠的损伤。
