Barrett C R, Bell A L, Ryan S F
Chest. 1979 Jun;75(6):705-11. doi: 10.1378/chest.75.6.705.
Structural and mechanical changes were correlated in 29 dogs with acute alveolar injury induced by the subcutaneous administration of N-nitroso-N-methylurethane (NNNMU). The injury was characterized by necrosis and repair of alveolar epithelium while the vascular endothelium remained essentially intact. Compliance of the lung (CL) decreased and elastic recoil increased as epithelial necrosis occurred. During recovery, improved elastic recoil coincided with epithelial regeneration, although CL remained abnormal. The late phase was characterized histologically by widespread closure of clusters of alveoli alternating with dilated small air spaces. The process resulted in distortion of lung architecture and resembled interstitial fibrosis. Reduced lung volume and decreased distensibility of dilated small air spaces may have accounted for the persistently abnormal CL. Because of the specific site of anatomic involvement, the predictable evolution of deranged lung mechanics, and the similarity to human lung injury (adult respiratory distress syndrome), the lung injured by administration of N-nitroso-N-methylurethane is a suitable model to study pathophysiology and types of therapy in a controlled setting.
对29只通过皮下注射N-亚硝基-N-甲基脲（NNNMU）诱导急性肺泡损伤的犬，研究其结构和力学变化的相关性。损伤表现为肺泡上皮坏死及修复，而血管内皮基本保持完整。随着上皮坏死的发生，肺顺应性（CL）降低，弹性回缩增加。在恢复过程中，弹性回缩改善与上皮再生同时出现，尽管CL仍异常。晚期组织学特征为肺泡群广泛闭合，与扩张的小气道间隙交替出现。该过程导致肺结构变形，类似间质性纤维化。肺容积减小和扩张的小气道间隙扩张性降低可能是CL持续异常的原因。由于解剖受累的特定部位、肺力学紊乱的可预测演变以及与人类肺损伤（成人呼吸窘迫综合征）的相似性，通过注射N-亚硝基-N-甲基脲造成损伤的肺是在可控环境下研究病理生理学和治疗类型的合适模型。
