Hotchkiss J A, Hilaski R, Cho H, Regan K, Spencer P, Slack K, Harkema J R
Department of Pathology, College of Veterinary Medicine, Michigan State University, East Lansing 48824-1317, USA.
Am J Respir Cell Mol Biol. 1998 Jan;18(1):91-9. doi: 10.1165/ajrcmb.18.1.2897.
Ozone (O3) is the principal oxidant pollutant in photochemical smog. Repeated exposures to O3 induces inflammation and mucous cell metaplasia in the nasal airways of laboratory animals. Our study was designed to determine the efficacy of a topical anti-inflammatory corticosteroid in preventing O3-induced rhinitis and mucous cell metaplasia in rat nasal epithelium. Male F344 rats were exposed to filtered air (0 ppm O3; air-controls) or 0.5 ppm O3, 8 h/day, for 3 or 5 days. Immediately before and after each exposure, rats received an intranasal instillation (50 microl/nasal passage) of a topical corticosteroid, fluticasone propionate (FP; 25 microg/nasal passage) or its vehicle only (0.01% ethanol in saline). Rats were killed 2 h after the third exposure (3-day exposure) or 3 days after the fifth exposure (5-day exposure) and nasal tissues were processed for light microscopy. Numeric densities of epithelial cells and neutrophils, and the amount of intraepithelial mucosubstances (IM) in the epithelium lining the maxilloturbinates were morphometrically determined. There were no significant differences in any measured parameter in air-exposed rats instilled with FP compared with air-exposed rats instilled with vehicle. Vehicle-treated rats exposed to ozone had neutrophilic rhinitis with 3.3- and 1.6-fold more intraepithelial neutrophils (3-day and 5-day exposure, respectively) and marked mucous cell metaplasia (5-day exposure only) with numerous mucous cells and approximately 60 times more IM in the nasal transitional epithelium compared with vehicle-treated air-controls. FP-treated rats exposed to ozone had minimal nasal inflammation (1.3-fold more intraepithelial neutrophils only after 3-day exposure) and minimal mucous cell metaplasia (5-fold more IM only after 5-day exposure) compared with vehicle-instilled, air-exposed rats. Results of this study indicate that FP-treatment is effective in attenuating not only O3-induced rhinitis (30-60% reduction) but also O3-induced mucous cell metaplasia (85% reduction) in rat nasal transitional epithelium. The cellular and molecular mechanisms involved in FP-induced attenuation of O3-induced nasal lesions remain to be determined.
臭氧（O₃）是光化学烟雾中的主要氧化污染物。反复接触O₃会诱发实验动物鼻气道的炎症和黏液细胞化生。我们的研究旨在确定局部抗炎皮质类固醇预防大鼠鼻上皮中O₃诱导的鼻炎和黏液细胞化生的效果。将雄性F344大鼠每天暴露于过滤空气（0 ppm O₃；空气对照组）或0.5 ppm O₃中，8小时/天，持续3天或5天。每次暴露前后，大鼠经鼻内滴注（50微升/鼻腔）局部皮质类固醇丙酸氟替卡松（FP；25微克/鼻腔）或仅其赋形剂（盐水中0.01%乙醇）。在第三次暴露后2小时（3天暴露组）或第五次暴露后3天（5天暴露组）处死大鼠，并对鼻组织进行光学显微镜检查。通过形态计量学确定上颌鼻甲上皮细胞和中性粒细胞的数量密度以及上皮内黏液物质（IM）的量。与滴注赋形剂的空气暴露大鼠相比，滴注FP的空气暴露大鼠的任何测量参数均无显著差异。与滴注赋形剂的空气对照组相比，暴露于臭氧的赋形剂处理大鼠出现嗜中性鼻炎，上皮内中性粒细胞分别增加3.3倍和1.6倍（3天和5天暴露组），并出现明显的黏液细胞化生（仅5天暴露组），鼻腔过渡上皮中有大量黏液细胞且IM增加约60倍。与滴注赋形剂的空气暴露大鼠相比，暴露于臭氧的FP处理大鼠的鼻炎症轻微（仅3天暴露后上皮内中性粒细胞增加1.3倍），黏液细胞化生轻微（仅5天暴露后IM增加5倍）。本研究结果表明，FP处理不仅能有效减轻大鼠鼻腔过渡上皮中O₃诱导的鼻炎（减少30 - 60%），还能减轻O₃诱导的黏液细胞化生（减少85%）。FP诱导减轻O₃诱导的鼻损伤所涉及的细胞和分子机制仍有待确定。
