Deslee G, Woods J C, Moore C M, Liu L, Conradi S H, Milne M, Gierada D S, Pierce J, Patterson A, Lewit R A, Battaile J T, Holtzman M J, Hogg J C, Pierce R A
Dept of Internal Medicine, Washington University School of Medicine, St Louis, MO, USA.
Service de Pneumologie CHU Reims, IFR53, Reims, France.
Eur Respir J. 2009 Aug;34(2):324-331. doi: 10.1183/09031936.00123008. Epub 2009 Apr 8.
Alveolar elastic fibres are key targets of proteases during the pathogenesis of chronic obstructive pulmonary disease (COPD). In the current study, we hypothesised that a response to injury leads to enhanced alveolar elastin gene expression in very severe COPD. Lung samples obtained from 43 patients, including 11 with very severe COPD (stage 4), 10 donors, 10 with moderate/severe COPD (stage 2-3) and 12 non-COPD subjects, were analysed for elastin mRNA expression by real-time RT-PCR and in situ hybridisation. Alveolar elastic fibres were visualised using Hart's staining of sections of frozen inflated lungs obtained from 11 COPD stage 4 patients and three donor lungs. Compared with donors, non-COPD and stage 2-3 COPD, elastin mRNA expression was significantly increased in very severe COPD lungs (12-fold change), and localised in situ hybridisation induced elastin expression to alveolar walls. Compared with donors, alveolar elastic fibres also comprised a greater volume fraction of total lung tissue in very severe COPD lungs (p<0.01), but elastic fibre content was not increased per lung volume, and desmosine content was not increased. The present study demonstrates enhanced alveolar elastin expression in very severe COPD. The efficiency of this potential repair mechanism and its regulation remain to be demonstrated.
在慢性阻塞性肺疾病（COPD）发病过程中，肺泡弹性纤维是蛋白酶的关键作用靶点。在本研究中，我们假设在极重度COPD中，损伤反应会导致肺泡弹性蛋白基因表达增强。我们通过实时逆转录聚合酶链反应（RT-PCR）和原位杂交技术，分析了43例患者的肺组织样本，其中包括11例极重度COPD患者（4期）、10例供体、10例中度/重度COPD患者（2-3期）以及12例非COPD受试者的弹性蛋白mRNA表达情况。使用Hart氏染色法对取自11例4期COPD患者和3例供体肺的冷冻充气肺切片进行观察，以显示肺泡弹性纤维。与供体、非COPD患者以及2-3期COPD患者相比，极重度COPD患者肺组织中的弹性蛋白mRNA表达显著增加（变化12倍），原位杂交显示弹性蛋白表达定位于肺泡壁。与供体相比，极重度COPD患者肺组织中肺泡弹性纤维在总肺组织中的体积分数也更高（p<0.01），但每单位肺体积的弹性纤维含量并未增加，异锁链素含量也未增加。本研究表明极重度COPD患者肺泡弹性蛋白表达增强。这种潜在修复机制的效率及其调控仍有待证实。
