Barth P J, Müller B, Wagner U, Bittinger A
Dept of Pathology, Philipps-Universität Marburg/Lahn, Germany.
Eur Respir J. 1995 Jul;8(7):1115-21. doi: 10.1183/09031936.95.08071115.
Nitrogen dioxide (NO2), the oxidation product of nitric oxide (NO), is a reactive free radical forming gas, the inhalation of which has been reported to induce severe damage to distal airways. In order to quantify dose and time course of parenchymal and vascular damage, rats were exposed to 5, 10 and 20 ppm NO2 for 3 and 25 days, followed by quantitative histology and morphometry of the lung. Histological investigations of the short-term exposed animals showed structural alterations extending from slight interstitial oedema after exposure to 5 ppm, to epithelial necrosis and interstitial inflammatory infiltration after exposure to 10 ppm, and an additional intra-alveolar oedema after 20 ppm. The pulmonary arteries disclosed no qualitative changes, such as muscularization of intra-acinar vessels. Long-term exposure to 10 ppm and 20 ppm NO2 resulted in emphysema and slight centrilobular interstitial fibrosis. Morphometric analysis revealed the alveolar surface density to be significantly diminished after short-term exposure to 20 ppm NO2 and long-term exposure to 10 and 20 ppm NO2. The medial thickness of pulmonary arteries was significantly increased after short- and long-term exposure to 20 ppm NO2 and long-term exposure to 10 ppm NO2. In the 5 ppm short- and long-term exposure groups the pulmonary arterial medial thickness was significantly decreased compared to controls. Correlation analysis revealed a negative correlation between average medial thickness and alveolar surface density (coefficient of correlation: -0.56). We conclude that the extent of NO2-induced pulmonary parenchymal and vascular alterations are closely related and concentration- and time-dependent.
二氧化氮（NO₂）是一氧化氮（NO）的氧化产物，是一种具有反应活性的自由基形成气体，据报道，吸入该气体会对远端气道造成严重损害。为了量化实质和血管损伤的剂量和时间进程，将大鼠暴露于5、10和20 ppm的NO₂中3天和25天，随后对肺进行定量组织学和形态计量学分析。对短期暴露动物的组织学研究显示，结构改变范围从暴露于5 ppm后的轻微间质水肿，到暴露于10 ppm后的上皮坏死和间质炎症浸润，以及暴露于20 ppm后出现的肺泡内水肿。肺动脉未发现定性变化，如腺泡内血管肌化。长期暴露于10 ppm和20 ppm的NO₂会导致肺气肿和轻微的小叶中心间质纤维化。形态计量学分析显示，短期暴露于20 ppm NO₂以及长期暴露于10 ppm和20 ppm NO₂后，肺泡表面密度显著降低。短期和长期暴露于20 ppm NO₂以及长期暴露于10 ppm NO₂后，肺动脉中膜厚度显著增加。在5 ppm短期和长期暴露组中，与对照组相比，肺动脉中膜厚度显著降低。相关性分析显示，平均中膜厚度与肺泡表面密度之间呈负相关（相关系数：-0.56）。我们得出结论，NO₂诱导的肺实质和血管改变程度密切相关，且与浓度和时间有关。
