Salmon M, Koto H, Lynch O T, Haddad E B, Lamb N J, Quinlan G J, Barnes P J, Chung K F
Thoracic Medicine, Imperial College School of Medicine at the National Heart and Lung Institute, London, United Kingdom.
Am J Respir Crit Care Med. 1998 Mar;157(3 Pt 1):970-7. doi: 10.1164/ajrccm.157.3.9704067.
Ozone is an environmental pollutant with potent oxidizing properties. We investigated whether exposure to ozone-induced cell proliferation in the lungs of rats, and determined the effect of an antioxidant and of a glucocorticosteroid in Brown-Norway (BN) rats. Following single ozone exposure (0.5, 1.0, or 3.0 ppm for 6 h), proliferating cell nuclear antigen (PCNA) expression, as determined with immunohistochemistry, was significantly increased in the bronchial epithelium and alveolar epithelium as compared with controls exposed to filtered air with a maximal effect at 24 to 48 h (p < 0.001). Apocynin (5 mg/kg, orally), a reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor, reduced the PCNA index in bronchial epithelium induced by ozone (3 ppm, 6 h) from 11.5 +/- 1.3% (percent of nuclear cells expressing PCNA) to 4.4 +/- 1.3% (mean +/- SEM; p < 0.05). Dexamethasone (3 mg/kg, intraperitoneally) also reduced the PCNA index in bronchial epithelium, from 19.2 +/- 2.3% to 10.9 +/- 2.6% (p < 0.05). Dexamethasone but not apocynin inhibited ozone-induced neutrophil influx. Rats exposed repeatedly to ozone (3.0 ppm, 3 h, on three occasions 48 h apart) expressed a lower PCNA index in bronchial epithelium than did rats exposed only once at 1.9 +/- 0.7% versus 6.0 +/- 0.9%, respectively (p < 0.05). The proliferative epithelial response following a single exposure to ozone is modulated through oxidative and inflammatory mechanisms probably involving neutrophils.
臭氧是一种具有强氧化特性的环境污染物。我们研究了臭氧暴露是否会诱导大鼠肺部细胞增殖，并确定了抗氧化剂和糖皮质激素对褐家鼠（BN大鼠）的影响。单次臭氧暴露（0.5、1.0或3.0 ppm，持续6小时）后，通过免疫组织化学测定，与暴露于过滤空气的对照组相比，支气管上皮和肺泡上皮中增殖细胞核抗原（PCNA）的表达显著增加，在24至48小时达到最大效应（p < 0.001）。阿朴吗啡（5 mg/kg，口服），一种还原型烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶抑制剂，可将臭氧（3 ppm，6小时）诱导的支气管上皮PCNA指数从11.5 +/- 1.3%（表达PCNA的细胞核细胞百分比）降至4.4 +/- 1.3%（平均值 +/- 标准误；p < 0.05）。地塞米松（3 mg/kg，腹腔注射）也降低了支气管上皮的PCNA指数，从19.2 +/- 2.3%降至10.9 +/- 2.6%（p < 0.05）。地塞米松而非阿朴吗啡抑制了臭氧诱导的中性粒细胞流入。反复暴露于臭氧（3.0 ppm，3小时，每隔48小时进行三次）的大鼠支气管上皮中的PCNA指数低于仅暴露一次的大鼠，分别为1.9 +/- 0.7%和6.0 +/- 0.9%（p < 0.05）。单次暴露于臭氧后的增殖性上皮反应可能通过涉及中性粒细胞的氧化和炎症机制进行调节。
