Voswinckel R, Motejl V, Fehrenbach A, Wegmann M, Mehling T, Fehrenbach H, Seeger W
Dept of Internal Medicine, University of Giessen, Giessen, Germany.
Eur Respir J. 2004 Oct;24(4):524-32. doi: 10.1183/09031936.04.10004904.
A model of inducible expansion of the gas exchange area in adult mice would be ideal for the investigation of molecular determinants of airspace regeneration in vivo. Therefore, the post-pneumonectomy (post-PNX) compensatory lung growth in adult C57BL/6 mice was characterised in this study. Mice underwent left-sided PNX. Right lung volume was assessed on days 1, 3, 5, 7, 10 and 21 after PNX, and total DNA and cellular proliferation of the right lung were determined. Lung histology was studied using immunohistochemistry and quantitatively characterised by detailed stereological investigations. Pulmonary function was assessed using a mouse body-plethysmograph. Following PNX, right-lung volume rapidly restored the initial volume of left and right lung. Total DNA increased significantly over 21 days and equalled the total DNA amount of both lungs in the control mice. Septal cell proliferation significantly increased after PNX, and included endothelial cells, epithelial cells, smooth muscle cells and fibroblasts. Stereological investigations of left and right control lungs versus right lungs 21 days after PNX indicated complete restoration of body mass-specific alveolar surface area. Pulmonary function testing showed marked alteration at 3 days and normalisation at 21 days post-PNX. In conclusion, well reproducible reconstitution of alveolar gas-exchange surface based on septal tissue expansion may be provoked by pneumonectomy in adult mice.
建立成年小鼠气体交换面积诱导性扩张模型,将非常有助于在体内研究气腔再生的分子决定因素。因此,本研究对成年C57BL/6小鼠肺切除术后的代偿性肺生长进行了表征。小鼠接受左侧肺切除术。在肺切除术后第1、3、5、7、10和21天评估右肺体积,并测定右肺的总DNA和细胞增殖情况。采用免疫组织化学方法研究肺组织学,并通过详细的体视学研究进行定量表征。使用小鼠体容积描记仪评估肺功能。肺切除术后,右肺体积迅速恢复到左、右肺的初始体积。总DNA在21天内显著增加,与对照小鼠双肺的总DNA量相等。肺切除术后,间隔细胞增殖显著增加,包括内皮细胞、上皮细胞、平滑肌细胞和成纤维细胞。对左、右对照肺与肺切除术后21天的右肺进行体视学研究表明,单位体重肺泡表面积完全恢复。肺功能测试显示,肺切除术后3天有明显改变,21天恢复正常。总之,成年小鼠肺切除可引发基于间隔组织扩张的、可良好重现的肺泡气体交换表面重建。