Chang L Y, Stockstill B L, Ménache M G, Mercer R R, Crapo J D
Duke University Medical Center, Department of Medicine, Durham, NC 27710, USA.
Res Rep Health Eff Inst. 1995 Mar(65 Pt 8-9):3-39; discussion 99-110.
Morphometric techniques were used to examine cellular and tissue changes occurring in male and female rat lungs exposed to ozone for a prolonged time. F344/N rats were exposed to 0.0, 0.12, 0.5, or 1.0 parts per million (ppm)* ozone for six hours per day, five days per week, for 20 months. Changes in cell volume, cell surface ratios, and cellular characteristics were studied in the terminal bronchioles and in the proximal alveolar regions of the lungs. Animals exposed for 20 months to 0.5 or 1.0 ppm ozone demonstrated dramatic increases in the volume of interstitium and epithelium along the alveolar ducts. The thickening of the epithelium was caused by an epithelial metaplasia in which the normal squamous epithelium was modified to a cuboidal epithelium similar, but not identical, to the type found in terminal bronchioles. This bronchiolar epithelial metaplasia was directly related to dose of ozone, and was characterized by differentiated ciliated cells and Clara cells similar to those found in terminal bronchioles; undifferentiated cuboidal cells also were found in the animals exposed to 0.5 and 1.0 ppm ozone. A mild fibrotic response was seen in the animals exposed to 1.0 ppm ozone, with increases in both the interstitial matrix and cellular interstitium. The individual components of the interstitial matrix, including collagen, elastin, basement membrane, and acellular spaces, all were increased. The increase in cellular interstitium was due to an increase in the volume of interstitial fibroblasts. A slight inflammatory response, identified by an increase in alveolar macrophages, was observed in the animals exposed to 1.0 ppm. The terminal bronchioles were less affected than the proximal alveolar region by the ozone exposures, which may indicate a resistance of this tissue to ozone damage. The changes in the terminal bronchioles mainly consisted of a shift in cell type from ciliated to Clara cells in the animals exposed to 1.0 ppm ozone. The bronchiolar epithelial metaplasia observed in the proximal alveolar ducts may indicate that a protective mechanism develops in response to prolonged exposure to high concentrations of ozone.
采用形态测量技术研究长期暴露于臭氧环境下的雄性和雌性大鼠肺部细胞及组织的变化。将F344/N大鼠每天暴露于0.0、0.12、0.5或1.0百万分之一（ppm）*的臭氧环境中，每周5天，每天6小时，持续20个月。研究了肺终末细支气管和近端肺泡区域的细胞体积、细胞表面积比及细胞特征的变化。暴露于0.5或1.0 ppm臭氧环境20个月的动物，其肺泡管周围的间质和上皮体积显著增加。上皮增厚是由上皮化生引起的，正常的鳞状上皮转变为立方上皮，类似于但不完全等同于终末细支气管中的上皮类型。这种细支气管上皮化生与臭氧剂量直接相关，其特征是存在与终末细支气管中相似的分化纤毛细胞和克拉拉细胞；暴露于0.5和1.0 ppm臭氧的动物中还发现了未分化的立方细胞。暴露于1.0 ppm臭氧的动物出现轻度纤维化反应，间质基质和细胞间质均增加。间质基质的各个成分，包括胶原蛋白、弹性蛋白、基底膜和无细胞间隙，均有所增加。细胞间质增加是由于间质成纤维细胞体积增大。暴露于1.0 ppm的动物出现轻微炎症反应，表现为肺泡巨噬细胞增多。臭氧暴露对终末细支气管的影响小于近端肺泡区域，这可能表明该组织对臭氧损伤具有抵抗力。暴露于1.0 ppm臭氧的动物，终末细支气管的变化主要是细胞类型从纤毛细胞转变为克拉拉细胞。在近端肺泡管中观察到的细支气管上皮化生可能表明，机体对长期暴露于高浓度臭氧会产生一种保护机制。
