静脉注射不同剂量博莱霉素诱导小鼠肺纤维化的比较研究

摘要

Objective To establish a mouse model of pulmonary fibrosis by using an improved program. Methods C57/BL6 male mice were randomly divided into the single-dose group and the multiple-dose group.The single-dose group were randomly divided into the groups of 1 00,1 50,200 mg/kg and the control group 1 .The multi-ple-dose group were randomly divided into the 50 mg/kg group and the control group 2.Their pathology of each lungs,immunohistochemistry of Col-Ⅰ,TGF-β1 andα-SMA were analyzed.Results The level of alveolitis reached the highest point at the second week in the single-dose group (P<0.01 ),and the level of pulmonary fibrosis reached the highest at the second and fourth weeks,respectively (P<0.01 ).In the 50mg/kg group,the levels of alveolitis and fibrosis peaked at the 1 0th week (P<0.05 ).TGF-β1 and α-SMA increased significantly in parts of alveolitis and pulmonary fibrosis.Conclusion In an intravenous delivery,a single dose of 200 mg/kg bleomycin can effec-tively reproduce pulmonary fibrosis.%目的：寻求建立小鼠肺纤维化模型的改良方案。方法雄性C57BL／6小鼠随机分为单次和多次注射模型组。单次注射模型组分为博莱霉素100、150、200 mg／kg组及对照组1；多次注射模型组分为博莱霉素50 mg／kg组及对照组2。取小鼠肺组织行病理检查，免疫组化检测肺Ⅰ型胶原蛋白、TGF-β1和α-SMA的表达。结果在单次注射模型组中，100、150、200 mg／kg组的肺泡炎均于第2周达峰（P＜0.01）；肺纤维化分别在第2、4、4周达峰（P＜0.01）。在多次注射模型组中，50 mg／kg组肺泡炎和肺纤维化均在第10周达峰（P＜0.05）。TGF-β1和α-SMA在肺泡炎和纤维化部位表达明显增加。结论尾静脉单次注射博莱霉素200 mg／kg可有效诱导肺纤维化，复制一个相对稳定的肺纤维化模型。