中国组织工程研究2017，Vol.21Issue(4)：512-519,8.DOI:10.3969/j.issn.2095-4344.2017.04.004
腹腔注射博来霉素诱导小鼠肺纤维化模型的长期稳定性
Intraperitoneal injection of bleomycin induces pulmonary fibrosis in mice:a long-term stability evaluation
摘要
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, fol owed 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 gradual y 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 col agen 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 factorβ1 (TGF-β1) andα-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 col agen, 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, al above indicators reached the highest level at the 2nd week, but gradual y decreased thereafter. At the 4th week, the expression Levels of TGF-β1 andα-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 col agen 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. Subject headings:Disease Models, Animal;Pulmonary Fibrosis;Bleomycin关键词
组织构建/组织工程/肺纤维化/转化生长因子β1/特发性肺间质纤维化/普通间质性肺炎/博来霉素/腹腔注射/小鼠/动物模型/动物实验/国家自然科学基金分类
医药卫生引用本文复制引用
苏敏红,江宁,李洪涛,王振国,谢玉芬,郑晓滨,涂常力,黄瑾..腹腔注射博来霉素诱导小鼠肺纤维化模型的长期稳定性[J].中国组织工程研究,2017,21(4):512-519,8.基金项目
国家自然科学基金项目(81470220) （81470220）
