Demnati R, Fraser R, Martin J G, Plaa G, Malo J L
Department of Chest Medicine, Hôpital du Sacré-Coeur, Montreal, Quebec, Canada.
Toxicol Sci. 1998 Oct;45(2):242-6. doi: 10.1006/toxs.1998.2532.
We assessed the effects of dexamethasone on functional and histological changes after acute exposure to a high level of chlorine gas in an animal model of reactive airways dysfunction syndrome (RADS). Sprague-Dawley male rats were exposed to 1500 ppm of chlorine for 5 min and treated with either dexamethasone (dex; 300 micrograms/kg/day) or saline intraperitoneally for 7 days. Lung resistance (RL), airway responsiveness to inhaled methacholine (MCh), airway wall morphometric measurements, and bronchoalveolar lavage (BAL) cells were assessed over a 2-week period after exposure. Dex administration significantly attenuated both chlorine-induced increased RL and chlorine-induced increased responsiveness to methacholine compared with saline: -2.7 +/- 6.8% vs 102.3 +/- 36.6% change from baseline RL (P < 0.01) and 2.5 +/- 0.6 mg/ml vs 1.2 +/- 0.7 mg/ml in the MCh concentration required to double the RL from baseline (P < 0.01). There was a tendency, albeit nonsignificant, for improvement in some indices of epithelial injury. Dex significantly attenuated the postexposure neutrophilic cellular response in BAL 1 day after exposure (15.8 +/- 4.9% neutrophils in the dex group vs 49.8 +/- 2.7% neutrophils in the saline group) (P < or = 0.001). Our results show that dex administration helps maintain pulmonary function, reduces BAL inflammatory cell number, and tends to improve some morphometric airway wall structure parameters in rats exposed to chlorine.
我们在反应性气道功能障碍综合征(RADS)动物模型中评估了地塞米松对急性暴露于高浓度氯气后功能和组织学变化的影响。将Sprague-Dawley雄性大鼠暴露于1500 ppm的氯气中5分钟,然后腹腔注射地塞米松(dex;300微克/千克/天)或生理盐水,持续7天。在暴露后的2周内评估肺阻力(RL)、对吸入乙酰甲胆碱(MCh)的气道反应性、气道壁形态学测量以及支气管肺泡灌洗(BAL)细胞。与生理盐水相比,给予地塞米松显著减轻了氯气诱导的RL增加和氯气诱导的对乙酰甲胆碱反应性增加:与基线RL相比变化为-2.7±6.8%,而生理盐水组为102.3±36.6%(P<0.01);使RL从基线翻倍所需的MCh浓度,地塞米松组为2.5±0.6毫克/毫升,生理盐水组为1.2±0.7毫克/毫升(P<0.01)。上皮损伤的一些指标有改善的趋势,尽管不显著。地塞米松显著减轻了暴露后1天BAL中的中性粒细胞反应(地塞米松组中性粒细胞为15.8±4.9%,生理盐水组为49.8±2.7%)(P≤0.001)。我们的结果表明,给予地塞米松有助于维持肺功能,减少BAL中的炎症细胞数量,并倾向于改善暴露于氯气的大鼠气道壁形态学结构参数。