Xisto Debora G, Farias Luciana L, Ferreira Halina C, Picanço Miguel R, Amitrano Daniel, Lapa E Silva Jose R, Negri Elnara M, Mauad Thais, Carnielli Denise, Silva Luiz Fernando F, Capelozzi Vera L, Faffe Debora S, Zin Walter A, Rocco Patricia R M
Universidade Federal do Rio de Janeiro, Instituto de Biofísica Carlos Chagas Filho - C.C.S., Laboratório de Investigação Pulmonar, Ilha do Fundão, 21949-900 - Rio de Janeiro - RJ, Brazil.
Am J Respir Crit Care Med. 2005 Apr 15;171(8):829-37. doi: 10.1164/rccm.200408-997OC. Epub 2005 Jan 18.
This study tested the hypotheses that chronic allergic inflammation induces not only bronchial but also lung parenchyma remodeling, and that these histologic changes are associated with concurrent changes in respiratory mechanics. For this purpose, airway and lung parenchyma remodeling were evaluated by quantitative analysis of collagen and elastin, immunohistochemistry (smooth-muscle actin expression, eosinophil, and dendritic cell densities), and electron microscopy. In vivo (airway resistance, viscoelastic pressure, and static elastance) and in vitro (tissue elastance, resistance, and hysteresivity) respiratory mechanics were also analyzed. BALB/c mice were sensitized with ovalbumin and exposed to repeated ovalbumin challenges. A marked eosinophilic infiltration was seen in lung parenchyma and in large and distal airways. Neutrophils, lymphocytes, and dendritic cells also infiltrated the lungs. There was subepithelial fibrosis, myocyte hypertrophy and hyperplasia, elastic fiber fragmentation, and increased numbers of myofibroblasts in airways and lung parenchyma. Collagen fiber content was increased in the alveolar walls. The volume proportion of smooth muscle-specific actin was augmented in distal airways and alveolar duct walls. Airway resistance, viscoelastic pressure, static elastance, and tissue elastance and resistance were significantly increased. In conclusion, prolonged allergen exposure induced remodeling not only of the airway wall but also of the lung parenchyma, leading to in vivo and in vitro mechanical changes.
慢性过敏性炎症不仅会导致支气管重塑，还会引起肺实质重塑，且这些组织学变化与呼吸力学的同时改变相关。为此，通过对胶原蛋白和弹性蛋白进行定量分析、免疫组织化学（平滑肌肌动蛋白表达、嗜酸性粒细胞和树突状细胞密度）以及电子显微镜检查来评估气道和肺实质重塑。还分析了体内（气道阻力、粘弹性压力和静态弹性）和体外（组织弹性、阻力和滞后性）的呼吸力学。用卵清蛋白致敏BALB/c小鼠，并使其反复接触卵清蛋白激发。在肺实质以及大气道和远端气道中可见明显的嗜酸性粒细胞浸润。中性粒细胞、淋巴细胞和树突状细胞也浸润到肺部。气道和肺实质出现上皮下纤维化、肌细胞肥大和增生、弹性纤维断裂以及肌成纤维细胞数量增加。肺泡壁中的胶原纤维含量增加。远端气道和肺泡管壁中平滑肌特异性肌动蛋白的体积比例增大。气道阻力、粘弹性压力、静态弹性以及组织弹性和阻力均显著增加。总之，长期暴露于过敏原不仅会导致气道壁重塑，还会引起肺实质重塑，进而导致体内和体外的力学变化。
