Fleischman R W, Baker J R, Thompson G R, Schaeppi U H, Illievski V R, Cooney D A, Davis R D
Thorax. 1971 Nov;26(6):675-82. doi: 10.1136/thx.26.6.675.
The intravenous administration of Bleomycin to 10 dogs at different dosages resulted in varying degrees of interstitial pneumonia in all cases and a lower incidence of nephrosis, foot pad excoriation and ulceration, onychoptosis, and alopecia. Pulmonary changes did not occur as a simple dose-related phenomenon. The lesions required at least 38 days to become apparent and appeared to increase in severity with time. Even at the lowest dose used (0·625 mg/kg body weight) very severe changes were seen 128 days after cessation of therapy. Morphological features of interstitial pneumonia were subpleural localization, focal mesothelial hyperplasia, marked hyperplasia and metaplasia of type II pneumocytes, fetalization of alveoli, and a pleomorphic inflammatory infiltrate. In cross-sections of lung lobes selected for histology approximately 1 to 22% of the parenchyma contained lesions. Involved areas showed marked elastosis, excess of reticular fibres, fibrosis, and increased acid mucopolysaccharides. The administration of Bleomycin produced pulmonary changes similar in many respects to those reported in busulphan-treated patients and desquamative interstitial pneumonia. The finding of interstitial pneumonia and pulmonary fibrosis in dogs treated with low doses over prolonged periods points the need to monitor pulmonary function in humans treated with Bleomycin.
对10只犬静脉注射不同剂量的博来霉素,所有病例均出现不同程度的间质性肺炎,肾病、脚垫剥脱和溃疡、脱甲症及脱毛的发生率较低。肺部变化并非简单的剂量相关现象。病变至少需要38天才能显现,且似乎随时间推移而加重。即使使用最低剂量(0·625毫克/千克体重),在治疗停止128天后也可见非常严重的变化。间质性肺炎的形态学特征为胸膜下定位、局灶性间皮细胞增生、II型肺泡上皮细胞显著增生和化生、肺泡胎儿化以及多形性炎性浸润。在选取用于组织学检查的肺叶横切面上,约1%至22%的实质组织有病变。受累区域表现出明显的弹性组织变性、网状纤维增多、纤维化以及酸性粘多糖增加。博来霉素的给药所产生的肺部变化在许多方面与白消安治疗患者及脱屑性间质性肺炎中所报告的变化相似。长期低剂量使用博来霉素治疗的犬出现间质性肺炎和肺纤维化,这表明对接受博来霉素治疗的人类需要监测肺功能。