致敏豚鼠咳嗽反应与气道炎症的关系

摘要

目的:研究致敏豚鼠不同强度的嗜酸细胞气道炎症对咳嗽反应的作用.方法: 卵蛋白致敏豚鼠34只,分成致敏对照组(7只)、低浓度卵蛋白组(7只)、中浓度卵蛋白组(8只)和高浓度卵蛋白组(12只),分别雾化吸入生理盐水、0.04%、0.2%和1%卵蛋白溶液激发.24 h后,比较各组豚鼠吸入辣椒素溶液诱导的咳嗽反应,气道对乙酰甲胆碱的反应性(PC150)和支气管肺泡灌洗液的细胞数量及成分.结果:致敏对照组和低浓度卵蛋白组无豚鼠死亡,而中浓度卵蛋白组和高浓度卵蛋白组激发后分别有1只和5只豚鼠因严重喘息发作死亡.随激发的卵蛋白浓度增高,吸入辣椒素溶液诱发的咳嗽频率从致敏对照组豚鼠的(6±2)次/3 min增加到在高浓度卵蛋白组的(22±4)次/3 min(P＜0.05);低浓度卵蛋白组的PC150无明显改变,中浓度和高浓度卵蛋白组明显降低,伴有支气管肺泡灌洗液中的细胞数量和嗜酸细胞比例增加.豚鼠的咳嗽反应与支气管肺泡灌洗液中细胞总数及嗜酸细胞比例存在显著的正相关(分别为r=0.84和0.78,P＜0.01),与PC150存在显著的负相关(r=-0.78,P＜0.01).PC150与支气管肺泡灌洗液中细胞总数及嗜酸细胞比例存在显著的负相关(分别为r=-0.80和-0.85,P＜0.01). 结论: 致敏豚鼠的咳嗽反应随嗜酸细胞性气道炎症加重而加大,并最终从咳嗽向喘息发展.%AIM: To investigate the effects of intensity of eosinophilic airway inflammation on cough response in guinea pigs sensitized and challenged with ovalbumin. METHODS: 34 sensitized guinea pigs were challenged with the aerosol of either saline (group A, n=7) or 0.04% (group B, n=7), 0.2% (group C, n=8) and 1% (group D, n=12) of ovalbumin. 24 hours later, cough response to inhaled capsaicin and airway responsiveness to inhaled methacholine (PC150) were measured. Total cell number and differentials in bronchoalveolar lavage were analyzed. RESULTS: After challenge, one animal in group C and five animals in group D died from severe wheezing. With ascending concentration of ovalbumin, cough frequency induced by inhaled capsaicin increased from (6±2) times/3 min in group A to (22±4) times/3 min in group D( P＜0.05). PC150, which did not change in group B, increased in both group C and group D significantly in addition to an increase in total cell number and eosinophils in bronchoalveolar lavage. Cough response to inhaled capsaicin was positively correlated with total cell number (r=0.84,P＜0.01) and eosinophils (r=0.78,P＜0.01) in bronchoalveolar lavage, and negatively correlated with PC150(r=-0.78,P＜0.01). There was a negative correlation between PC150 and total cell number (r=-0.80,P＜0.01) or eosinophils (r=-0.85,P＜0.01). CONCLUSION: Cough response in sensitized guinea pigs is enhanced and finally develops into wheezing with a progress in eosinophilic airway inflammation.