博莱霉素诱导α平滑肌肌动蛋白Cre重组酶转基因小鼠肺纤维化上皮细胞-间质转分化的研究

Detection of Epithelial to Mesenchymal Transition in Airways of a Bleomycin Induced Pulmonary Fibrosis Model Derived From an α-Smooth Muscle Actin-Cre Transgenic Mouse

目的探讨在博莱霉素诱导的肺纤维化中是否发生了上皮细胞-间质转分化(EMT)现象,支气管上皮细胞是否参与了这一过程。方法采用α平滑肌肌动蛋白Cre重组酶转基因小鼠(α-SMA-Cre/R26R双转基因鼠)为实验动物,构建博莱霉素诱导的小鼠肺纤维化模型,进行组织X-gal染色和α平滑肌肌动蛋白免疫荧光检测。结果气管内灌注博莱霉素的转基因小鼠支气管上皮下部分X-gal蓝染明显增多,终末小气道周围和肺血管壁蓝染细胞出现或增多,部分地区出现了支气管周围肺泡上皮细胞(ACE)阳性蓝染和浸润。结论在博莱霉素诱导的肺纤维化小鼠模型中可以观察到EMT现象,气道上皮细胞和肺泡上皮细胞能向间充质细胞转化,参与肺纤维化病理过程。

Objective To explore whether epithelial to mesenchymal transition （EMT） occurs in bleomycin（BLM） induced pulmonary fibrosis, and the involvement of bronchial epithelial cells （BECs） in the EMT. Methods BLM-induced peribronchial fibrosis in an α-smooth muscle actin-Cre transgeuic mouse （ α-SMA- Cre/R26R） was examined by pulmonary βgal staining and α-SMA immunofluorescence staining. Results BLM-treated mice showed significantly enhanced βgal staining in subepithelial areas in bronchi, terminal bronchioles and walls of pulmonary vessels. Some alveolar epithelial cells （AECs） in certain peribronchial areas or even a small subset of BECs were also positively stained, as confirmed by α-SMA immunostaining. Conclusions EMT occurs in BLM-induced peribronchial fibrosis mice. BECs,like AECs, have the capacity to undergo EMT and to contribute to mesenchymal expansion in pulmonary fibrosis.