Tryka A F, Skornik W A, Godleski J J, Brain J D
Am Rev Respir Dis. 1982 Dec;126(6):1074-9. doi: 10.1164/arrd.1982.126.6.1074.
The effects of a single intratracheal instillation of bleomycin followed by exposure to 70% oxygen for 72 h were studied in hamsters. Mortality increased markedly among hamsters exposed to 70% oxygen for 72 h after bleomycin instillation, compared with animals receiving bleomycin and breathing room air. The lethal dose required to kill 50% of the hamsters at 30 days (LD50, 30 day) for bleomycin alone was 0.73 U/100 g body weight, whereas the LD50, 30 day for bleomycin followed by 70% oxygen fell to 0.23 U/100 g body weight. Using morphometry and light microscopy, we found that the amount of diseased lung increased in hamsters given bleomycin with hyperoxia compared with that in those treated with bleomycin alone. After 0.20 U bleomycin and air, 2.8 +/- 1.6% of the lung was abnormal, but with 0.20 U bleomycin followed by 70% oxygen, 42.7 +/- 17.9% of the lung was abnormal. At bleomycin doses that produced no apparent lesions, the addition of 70% oxygen for 72 h produced focal interstitial fibrosis at 30 days. Neither mortality nor significant histologic changes were seen in hamsters treated with saline followed by exposure to 70% oxygen for 72 h. This study demonstrates that hyperoxia potentiates bleomycin damage and suggests that the use of elevated oxygen concentrations in patients being treated with bleomycin should be minimized.
在仓鼠中研究了单次气管内滴注博来霉素后再暴露于70%氧气72小时的影响。与接受博来霉素并呼吸室内空气的动物相比，博来霉素滴注后暴露于70%氧气72小时的仓鼠死亡率显著增加。单独使用博来霉素时，在30天内杀死50%仓鼠所需的致死剂量（LD50，30天）为0.73 U/100 g体重，而博来霉素后再暴露于70%氧气时，LD50，30天降至0.23 U/100 g体重。使用形态计量学和光学显微镜，我们发现与单独接受博来霉素治疗的仓鼠相比，给予博来霉素并吸入高氧的仓鼠患病肺组织量增加。给予0.20 U博来霉素并呼吸空气后，2.8±1.6%的肺组织异常，但给予0.20 U博来霉素后再暴露于70%氧气，42.7±17.9%的肺组织异常。在未产生明显病变的博来霉素剂量下，添加70%氧气72小时在30天时会产生局灶性间质纤维化。用生理盐水处理后再暴露于70%氧气72小时的仓鼠既未出现死亡率增加，也未出现明显的组织学变化。本研究表明高氧会增强博来霉素的损伤作用，并提示在用博来霉素治疗的患者中应尽量减少高氧浓度的使用。
