Costa D L, Tepper J S, Stevens M A, Watkinson W P, Doerfler D L, Gelzleichter T R, Last J A
Health Effects Research Laboratory, United States Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.
Am J Respir Crit Care Med. 1995 May;151(5):1512-8. doi: 10.1164/ajrccm.151.5.7735608.
The potential for irreversible lung impairment resulting from life-long ozone (O3) exposure remains uncertain. To address this question, young adult rats (male, F-344) were exposed to a simulated urban profile of O3 for 1, 3, 13, 52, or 78 wk, after which pulmonary function tests were performed. To assess reversibility of effects, cohorts from the 13-, 52-, and 78-wk groups were evaluated, respectively, after an additional 6, 27, and 17 wk of clean air. Static and dynamic lung properties were based on measurements of lung volume apportionment, respiratory system compliance (Crs), DLCO, multibreath N2 washout, and maximum expiratory flow-volume relationships. Electrocardiography was also performed in unanesthetized, restrained rats after 52 and 78 wk, as were determinations of wet and dry lung weights, lung collagen, and associated connective tissue crosslinks. Small (< 10%) but significant reductions in TLC and RV were noted after 13, 52, and 78 wk of O3 exposure. At 13 and 52 wk, N2 washout was enhanced, though at 78 wk it was similar to control. None of these changes appeared progressive with continued O3 exposure. Post exposure to clean air did not completely reverse the reduction in TLC. Additionally, Crs, though not affected during O3 exposure, decreased during the air recovery. No O3-related changes in collagen were apparent, however. Thus, near life-long exposure of F-344 rats to a worse-case, urban profile of O3 appears to have led to a functionally restrictive, i.e. "stiffened," lung without overt fibrosis. Furthermore, certain aspects of the O3-induced effect were not fully reversible.
终身暴露于臭氧（O₃）导致不可逆肺损伤的可能性仍不确定。为解决这一问题，将年轻成年大鼠（雄性，F-344）暴露于模拟城市环境的O₃中1、3、13、52或78周，之后进行肺功能测试。为评估效应的可逆性，分别在13周、52周和78周组的大鼠再暴露于清洁空气6周、27周和17周后进行评估。静态和动态肺特性基于肺容积分配、呼吸系统顺应性（Crs）、一氧化碳弥散量（DLCO）、多次呼吸氮洗脱和最大呼气流量-容积关系的测量。在52周和78周后，还对未麻醉、受约束的大鼠进行了心电图检查，同时测定了肺湿重和干重、肺胶原蛋白以及相关结缔组织交联。暴露于O₃ 13周、52周和78周后，肺总量（TLC）和残气量（RV）出现了小幅度（<10%）但显著的降低。在13周和52周时，氮洗脱增强，而在78周时与对照组相似。随着O₃持续暴露，这些变化均未呈现进行性发展。暴露于清洁空气后，TLC的降低并未完全逆转。此外，Crs在O₃暴露期间虽未受影响，但在空气恢复期下降。然而，未观察到与O₃相关的胶原蛋白变化。因此，F-344大鼠近乎终身暴露于最坏情况的城市O₃环境中，似乎导致了功能性受限，即“僵硬”的肺，且无明显纤维化。此外，O₃诱导效应的某些方面并非完全可逆。
