Noninvasive measurement of airway responsiveness in allergic mice using barometric plethysmography
Noninvasive measurement of airway responsiveness in allergic mice using barometric plethysmography
复制标题
DOI：
10.1164/ajrccm.156.3.9606031
复制
发表时间：
1997-09-01
影响因子：
24.7
通讯作者：
Gelfand, EW
中科院分区：
文献类型：
--
作者：
Hamelmann, E;Schwarze, J;Gelfand, EW
为了研究过敏致敏后气道反应性（AR）增加的机制和动力学，动物模型非常有价值。使用气压全身体积描记法和增强暂停（Penh）的增加作为气道阻塞的指标，我们测量了意识清醒、不受约束的小鼠在用卵清蛋白（OVA）致敏和气道激发后对吸入乙酰甲胆碱的反应。与对照动物相比，致敏和受攻击的动物对雾化乙酰甲胆碱的 AR 显着增加。 Penh 测量的 AR 与 IgE 产生增加和嗜酸性粒细胞肺部浸润有关。在另一种方法中，我们使用气管切开小鼠证实了下呼吸道参与对雾化乙酰甲胆碱的反应。乙酰甲胆碱激发后 Penh 值的增加也与通过食管测量的胸膜内压力增加相关。最后，第二天使用侵入性技术对同一只动物进行测量时，使用非侵入性技术表现出 AR 的小鼠也表现出对雾化乙酰甲胆碱的肺部抵抗反应增加。用 β(2) 激动剂预处理小鼠可抑制 Penh 值的增加。这些数据表明，通过气压全身体积描记法测量吸入乙酰甲胆碱的 AR 是小鼠过敏致敏后气道高反应性的有效指标。在无约束、有意识的动物中测量 AR 为评估气道高反应性的发展和维持的机制和动力学以及评估各种治疗干预措施提供了新的机会。
To study the mechanisms and kinetics underlying the development of increased airway responsiveness (AR) after allergic sensitization, animal models have been invaluable. Using barometric wholebody plethysmography and increases in enhanced pause (Penh) as an index of airway obstruction, we measured responses to inhaled methacholine in conscious, unrestrained mice after sensitization and airway challenge with ovalbumin (OVA). Sensitized and challenged animals had significantly increased AR to aerosolized methacholine compared with control animals. AR measured as Penh was associated with increased IgE production and eosinophil lung infiltration. In a separate approach we confirmed the involvement of the lower airways in the response to aerosolized methacholine using tracheotomized mice. Increases in Penh values after methacholine challenge were also correlated with increased intrapleural pressure, measured via an esophageal tube. Lastly, mice demonstrating AR using a noninvasive technique also demonstrated increased pulmonary resistance responses to aerosolized methacholine when measured using an invasive technique the following day in the same animals. The increases in Penh values were inhibited by pretreatment of the mice with a beta(2)-agonist. These data indicate that measurement of AR to inhaled methacholine by barometric whole-body plethysmography is a valid indicator of airway hyperresponsiveness after allergic sensitization in mice. The measurement of AR in unrestrained, conscious animals provides new opportunities to evaluate the mechanisms and kinetics underlying the development and maintenance of airway hyperresponsiveness and to assess various therapeutic interventions.