Intravenous injection of bleomycin induces pulmonary fibrosis in mice: a stability evaluation

doi:10.3969/j.issn.2095-4344.2015.40.008

Abstract

Abstract:

BACKGROUND: It is particularly important to establish an ideal animal model of pulmonary fibrosis to investigate the underlying pathogenesis and screen effective drugs to prevent and control pulmonary fibrosis.

OBJECTIVE: To establish a modified scheme of establishing mouse models that can reflect pulmonary fibrosis formation in humans.

METHODS: Fifty-six male C57BL/6 mice were randomly divided into two groups: A (a single large-dose injection) and B (multiple small-dose injections). Mice in group A were subjected to a single intravenous injection of bleomycin 200 mg/kg via the tail vein; and mice in group B received intravenous injections of bleomycin 50 mg/kg via the tail vein per week, totally for 6 weeks.

RESULTS AND CONCLUSION: Micro-CT scan images showed that pulmonary manifestations at the 4^th week after modeling was the most representative in group A, including peri-pulmonary field and the grid-like shadows on the lung bottom, uneven patchy shadows, opaque shadow. The range of lung lesions was slightly decreased at the 6^th week. The pulmonary pathological changes displayed on CT scans of mice from the group B were similar to those in group A, but the pulmonary fibrosis was gradually aggravated with time. The scores of alveolitis and pulmonary fibrosis in group A reached the highest level at the 4^th week after modeling, and slightly decreased at the 6^th week, while in group B, the scores of alveolitis and pulmonary fibrosis were gradually increased after modeling, and higher than those in group A at the 6^th week. Immunohistochemistry showed that abnormal type I collagen deposition was mainly distributed in the subpleural region, peri-vascular region and alveolar septa, which was consistent with the distribution of collagen fibers displayed by Masson staining. The expression of transforming growth factor β1 and α smooth muscle actin in the regions developing alveolitis and pulmonary fibrosis was significantly increased. In group A, the expression of type I collagen, transforming growth factor β1 and α smooth muscle actin reached the peak level at the 4^th week after modeling, and slightly declined at the 6^th week. In group B, the expression of typeⅠcollagen, transforming growth factor β1 and α smooth muscle actin was gradually increased after modeling, and was higher than that in group A at the 6^th week. The hydroxyproline content in lung tissue of mice in group A reached the peak at the 4^th week after modeling, and slightly declined at the 6^th week, however, in B group, it was gradually increased after modeling, and was higher than that in group A at the 6^th week after modeling. These results demonstrate that (1) intravenous injection of bleomycin via the tail vein can effectively induce pulmonary fibrosis; (2) transforming growth factor β1 and α smooth muscle actin play an important role in the occurrence and development of pulmonary fibrosis; (3) mouse models of pulmonary fibrosis induced by multiple injections of small-dose bleomycin have more typical characteristics of usual interstitial pneumonia in particular better stability, and are more in line with the evolution of idiopathic pulmonary fibrosis than mouse models of pulmonary fibrosis-induced by a single injection of large-dose bleomycin.

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

Key words: Pulmonary Fibrosis, Bleomycin, Disease Models, Animal

CLC Number:

R318

Tu Chang-li, Liu Xiang, Zheng Xiao-bin, Yu Jia-lin, Zhu Shu-qin, Su Min-hong, Wu Wei-ming, Huang Jin. Intravenous injection of bleomycin induces pulmonary fibrosis in mice: a stability evaluation[J]. Chinese Journal of Tissue Engineering Research, 2015, 19(40): 6436-6443.

Figures/Tables 5

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