不同激发方式对小鼠过敏性支气管哮喘模型的影响

Effect of different challenge methods on a murine model of allergic asthma

目的探讨不同激发方式对小鼠过敏性支气管哮喘(简称哮喘)模型的影响。方法模型组用卵清蛋白致敏和激发BalB/c小鼠,第0天、第7天、第14天腹腔注射致敏,从第28天开始分别给予不同次数和方式的激发。根据激发方式的不同,随机分为5组,包括三次滴鼻激发组、二次雾化20min激发组、三次雾化20min激发组、三次雾化30min激发组、四次雾化20min激发组,每组12只。激发后48h采用整体体积描记法检测小鼠气道反应性,结果以增强的呼气间歇(enhanced pause,Penh)表示,测定肺功能后再用磷酸盐缓冲液对全肺进行支气管肺泡灌洗,支气管肺泡灌洗液(BALF)进行细胞学分析。结果哮喘组气道反应性(Penh%)和BALF中嗜酸粒细胞比例(EOS%)与正常组相比差异均有统计学意义(P<0.05)。三次滴鼻激发组EOS%和Penh%显著高于其他雾化激发组(P<0.05),其中BALF中EOS%三次滴鼻激发组(46.30±4.55)%,与二次雾化20min激发组(31.19±12.84)%、三次雾化20min激发组(29.00±12.33)%、四次雾化20min激发组(37.08±8.44)%相比有显著差异,与三次雾化30min激发组(41.17±8.78)%无显著差异。三次滴鼻激发组PC100[(3.75±1.79)g/L]和三次雾化30min激发组[(5.94±3.27)g/L]、四次雾化20min激发组[(5.19±1.88)g/L]有显著差异(P<0.05)。三次滴鼻激发组激发过程中动物死亡2只,其余各组均无死亡。结论滴鼻和雾化激发均能成功建立哮喘模型,其中滴鼻激发建立的哮喘模型气道炎症及气道反应性升高更为显著。

Objective To investigate the effect of different challenge methods on a murine model of allergic bronchial asthma（asthma）.Methods BalB/c mice were sensitized and challenged by ovalbumin（OVA）.Mice were administered by intraperitoneal antigen on days 0,7 and 14,and firstly challenged with OVA aerosol on days 28.They were divided into 5 groups by different challenge methods and time,including intranasal administration for 3 consecutive days,aerosol administrations for 20 minutes once a day for 2 consecutive days,20 minutes once a day for 3 consecutive days,30 minutes once a day for 3 consecutive days,20 minutes once a day for 4 consecutive days.Forty-eight hours after the last challenge,airway hyperreactivity to methacholine was evaluated by whole-body plethysmography,present as enhanced expiratory pause （Penh）.After the measure of Penh,lungs were lavaged with PBS.Bronchoalveolar lavage cytology was analysed.Results Airway hyperreactivity and eosinophilia of asthmatic mice as evaluated were significantly increased when compared with normal（P〈0.05）.Airway hyperreactivity and eosinophilia of the group of intranasal administration were significantly increased compared with those of other groups of aerosol challenge（P〈0.05）.Two mice died in the group of intranasal administration,there was no death in other groups.Conclusions Asthmatic model can be established successfully by both of nasal challenge and aerosol challenge,and the intranasal administration trigger more serious airway inflammation and hyperreactivity than aerosol challenge.