van Bree L, Dormans J A, Boere A J, Rombout P J
Laboratory of Health Effects Research, National Institute of Public Health and the Environment, PO Box 1, NL-3720 BA Bilthoven, The Netherlands.
Inhal Toxicol. 2001 Aug;13(8):703-18. doi: 10.1080/08958370126868.
The aim of this study was to investigate the time course of lung injury in rats during acute and subchronic ozone exposure and during postexposure recovery. Rats were continuously exposed to 0.4 ppm ozone ( approximately 0.8 mg O(3)/m(3)) for 1, 3, 7, 28, or 56 days. Recovery from 3 days of exposure was studied at day 7, 14, and 28; recovery from 7 days of exposure was studied at day 14, 28, and 56, recovery from 28 days of exposure was studied at day 35 and 56, and recovery from 56 days of exposure was studied at day 136. The study included a correlated biochemical and morphological analysis of inflammatory responses, structural changes, and collagen content. The acute inflammatory response, as measured by an increase of polymorphonuclear cells and plasma protein in bronchoalveolar lavage (BAL) fluid, reached a maximum at day 1 and resolved largely within 6 days during ongoing exposure. Numbers of macrophages in BAL fluid increased progressively up to day 56, and slowly returned to near control levels when exposure was followed by postexposure recovery. Histological examination and morphometry of the lungs revealed centriacinar inflammatory responses throughout ozone exposure. Centriacinar thickening of septa was observed at day 7. Ductular septa, thickened progressively at days 7, 28, and 56 of exposure, showed increased collagen upon exposure at day 28, which was further enhanced at exposure at day 56. Increased collagen content in lungs, as measured biochemically by hydroxyproline concentration, was observed at exposure day 56. Collagen content was not different from control at day 56 when 7 or 28 days of exposure was followed by postexposure recovery. After continuous ozone exposure, respiratory bronchioles were present in an increasing degree, and remained present after a recovery period. The results of this study clearly show that after continuous exposure to O(3) some acute effects, such as protein and albumin content, and neutrophil influx in BAL fluid, returned to control levels within a few days. However, other parameters, such as the alveolar macrophage response and structural changes such as the presence of terminal bronchioles, thickening of ductular septa by enhanced cellularity, and collagen formation, persisted or progressively increased during continued exposure. Postexposure recovery seems to partly resolve these subchronic responses (macrophages response, septal cellularity), whereas other effects (collagen increase and respiratory bronchioles formation) do not disappear.
本研究的目的是调查大鼠在急性和亚慢性臭氧暴露期间以及暴露后恢复过程中肺损伤的时间进程。将大鼠连续暴露于0.4 ppm臭氧（约0.8 mg O₃/m³）1、3、7、28或56天。研究了暴露3天后在第7、14和28天的恢复情况；暴露7天后在第14、28和56天的恢复情况；暴露28天后在第35和56天的恢复情况；暴露56天后在第136天的恢复情况。该研究包括对炎症反应、结构变化和胶原蛋白含量进行相关的生化和形态学分析。通过支气管肺泡灌洗（BAL）液中多形核细胞和血浆蛋白增加来衡量的急性炎症反应在第1天达到最大值，并在持续暴露的6天内基本消退。BAL液中巨噬细胞数量在第56天前逐渐增加，在暴露后恢复时缓慢恢复到接近对照水平。肺组织学检查和形态测量显示在整个臭氧暴露过程中存在中心腺泡炎症反应。在第7天观察到中心腺泡间隔增厚。在暴露的第7、28和56天，导管间隔逐渐增厚，在暴露第28天时显示胶原蛋白增加，在暴露第56天时进一步增强。通过羟脯氨酸浓度生化测量，在暴露第56天时观察到肺中胶原蛋白含量增加。在暴露7天或28天后进行暴露后恢复，在第56天时胶原蛋白含量与对照无差异。连续臭氧暴露后，呼吸性细支气管的出现程度增加，并且在恢复期后仍然存在。本研究结果清楚地表明，连续暴露于O₃后，一些急性效应，如BAL液中的蛋白质和白蛋白含量以及中性粒细胞流入，在几天内恢复到对照水平。然而，其他参数，如肺泡巨噬细胞反应和结构变化，如终末细支气管的存在、导管间隔因细胞增多而增厚以及胶原蛋白形成，在持续暴露期间持续存在或逐渐增加。暴露后恢复似乎部分解决了这些亚慢性反应（巨噬细胞反应、间隔细胞增多），而其他效应（胶原蛋白增加和呼吸性细支气管形成）并未消失。
