Wright J L, Postma D S, Kerstjens H A M, Timens W, Whittaker P, Churg A
Department of Pathology, University of British Columbia, Vancouver, British Columbia, Canada.
Inhal Toxicol. 2007 Sep;19(11):915-23. doi: 10.1080/08958370701515563.
Although small airway remodeling (SAR) leading to airflow obstruction is a common consequence of human cigarette smoking, the airways have been largely ignored in animal models of chronic obstructive pulmonary disease (COPD). We examined lung structure in a guinea pig model of chronic cigarette smoke exposure to ascertain whether smoke induced SAR, and to evaluate how these anatomic lesions correlate with physiologic changes. We used tissue from guinea pigs exposed to cigarette smoke or air for 6 mo. Pulmonary function tests were performed, and histologic sections were prepared. Airspace size (Lm) and changes in the structure of the small airways were evaluated by morphometric analysis. Chronic smoke exposure was associated with increased airway wall thickness and increased amounts of thick collagen fibers in the walls of the small airways, as well as with increased Lm. The increase in thick collagen fibers related negatively to peak expiratory volume (PEF) and the ratio of forced expiratory volume in 1 s to forced ventilatory capacity (FEV(0.1)/FVC), and positively to airway resistance. Physiologic lung volumes were predicted by airspace size, but residual volume (RV) and total lung capacity (TLC) also were related to airway wall thickness. Amounts of smooth muscle were not changed and did not predict any physiologic abnormalities. We conclude that cigarette smoke exposure results in SAR in the guinea pig, alterations that are reflected in increased airways resistance with diminished airflow and air trapping, mimicking human disease. This model should prove useful in further investigations into the mechanisms of airway remodeling.
尽管导致气流阻塞的小气道重塑（SAR）是人类吸烟的常见后果，但在慢性阻塞性肺疾病（COPD）的动物模型中，气道在很大程度上被忽视了。我们在慢性香烟烟雾暴露的豚鼠模型中检查了肺结构，以确定烟雾是否会诱发SAR，并评估这些解剖学病变与生理变化之间的关系。我们使用了暴露于香烟烟雾或空气6个月的豚鼠的组织。进行了肺功能测试，并制备了组织学切片。通过形态计量分析评估气腔大小（Lm）和小气道结构的变化。慢性烟雾暴露与气道壁厚度增加、小气道壁中粗胶原纤维数量增加以及Lm增加有关。粗胶原纤维的增加与呼气峰值容积（PEF）以及1秒用力呼气容积与用力肺活量之比（FEV(0.1)/FVC）呈负相关，与气道阻力呈正相关。生理肺容积可由气腔大小预测，但残气量（RV）和肺总量（TLC）也与气道壁厚度有关。平滑肌数量没有变化，也不能预测任何生理异常。我们得出结论，香烟烟雾暴露会导致豚鼠出现SAR，这些变化表现为气道阻力增加、气流减少和气体潴留，类似于人类疾病。该模型在进一步研究气道重塑机制方面应会证明是有用的。
