Borzone G, Moreno R, Urrea R, Meneses M, Oyarzún M, Lisboa C
Department of Respiratory Diseases and Medical Research Center, Pontificia Universidad Católica de Chile, and Program of Pathology, Institute of Biomedical Sciences, Universidad de Chile, Santiago, Chile.
Am J Respir Crit Care Med. 2001 Jun;163(7):1648-53. doi: 10.1164/ajrccm.163.7.2006132.
Administration of bleomycin into the lungs of experimental animals has been utilized as a model to understand human pulmonary fibrosis. Most of the studies, however, have focused on early stages of the lung reaction. We hypothesized that chronic stages of the model may not mimic idiopathic pulmonary fibrosis, since in preliminary studies, lung volume and compliance were not decreased. Eight male Sprague-Dawley rats receiving intratracheal bleomycin (0.5 U/100 g body weight) underwent measurement of FRC, inspiratory capacity, and lung compliance 120 d later. Lung histologic changes were evaluated using light microscopy. Eight rats without intervention served as controls. Results show that our model, in early stages, has histologic changes no different from those previously described elsewhere. In chronic stages, however, the model does not behave as a restrictive syndrome: FRC is normal or increased, whereas lung compliance is normal. Focal peribronchiolar inflammation and fibrosis associated with paracicatricial emphysematous changes are the main histologic features of long-term lung remodeling after bleomycin. We conclude that while the chronic stages of the model may be informative in understanding mechanisms of fibrosis, care should be taken not to extrapolate to human idiopathic pulmonary fibrosis. We speculate that the model might resemble a particular subgroup of human interstitial lung disease, namely, those involving peribronchiolar structures.
将博来霉素注入实验动物肺部已被用作一种模型来理解人类肺纤维化。然而，大多数研究都集中在肺部反应的早期阶段。我们推测该模型的慢性阶段可能无法模拟特发性肺纤维化，因为在初步研究中，肺容量和顺应性并未降低。八只接受气管内注射博来霉素（0.5 U/100 g体重）的雄性Sprague-Dawley大鼠在120天后进行了功能残气量（FRC）、吸气量和肺顺应性的测量。使用光学显微镜评估肺部组织学变化。八只未接受干预的大鼠作为对照。结果表明，我们的模型在早期阶段的组织学变化与其他地方先前描述的无异。然而，在慢性阶段，该模型并不表现为限制性综合征：功能残气量正常或增加，而肺顺应性正常。与瘢痕旁肺气肿变化相关的局灶性细支气管周围炎症和纤维化是博来霉素治疗后长期肺重塑的主要组织学特征。我们得出结论，虽然该模型的慢性阶段可能有助于理解纤维化机制，但应注意不要外推至人类特发性肺纤维化。我们推测该模型可能类似于人类间质性肺疾病的一个特定亚组，即那些涉及细支气管周围结构的疾病。
