Abstract
BACKGROUND: There is no effective drug for idiopathic pulmonary fibrosis (IPF), because of a lack of the animal model imitating the complete pathogenesis of human IPF. Therefore, it is critical to establish an ideal animal IPF model used for investigating the underlying pathogenesis and developing a kind of effective drug.
OBJECTIVE: To establish an animal model that can mimic more characters of human IPF.
METHODS: Seventy male C57BL/6 mice were randomly divided into two groups, followed by subjected to the intraperitoneal injection of bleomycin (35 mg/kg) on days 1, 4, 8, 11, 15, 18, 22, and 25, twice (group A) or once (group B) a week. Mice were sacrificed at 2, 4, 6, 8, and 10 weeks after the eighth injection, and the lung tissues were moved used for hematoxylin-eosin, Masson and immunohistochemical stainings.
RESULTS AND CONCLUSION: There were various degrees of alveolitis and pulmonary fibrosis in the two groups at different time points after the last injection. The scores of alveolitis and pulmonary fibrosis in the group A began to gradually increase from the 2nd week and reached the highest level at the 6th-8th weeks until the 10th week. In contrast, the scores of alveolitis and pulmonary fibrosis in the group B peaked at the 2nd week, then fluctuately decreased, and were significantly lower than those in the group A at the 6th week (P < 0.05). Immunohistochemistry showed that type I collagen deposition was mainly distributed in the subpleural region, peri-vascular region and alveolar septa, which was consistent with Masson staining findings. The expression levels of transforming growth factor β1 (TGF-β1) and α-smooth muscle actin (α-SMA) in the regions developing alveolitis and pulmonary fibrosis were significantly increased. In the group A, the expression levels of type I collagen, TGF-β1, α-SMA, and the hydroxyproline content in the lung tissues reached the peak level at 6-8 weeks. However, in the group B, all above indicators reached the highest level at the 2nd week, but gradually decreased thereafter. At the 4th week, the expression Levels of TGF-β1 and α-SMA in the group B were significantly lower than those in the group A (P < 0.05). At the 6th week, the hydroxyproline and type I collagen levels in the group B were significantly lower than those in the group A (P < 0.05). In conclusion, the mouse model of pulmonary fibrosis induced by intraperitoneal injection of 35 mg/kg bleomycin twice weekly can be used to mimic the repetitive wound healing process, pathological morphology and cytokine changes of human IPF, which is prone to administration, with better stability and repeatability. This model is of great significance for the study on IPF.
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