呼吸道变应性炎性反应小鼠模型的建立  

Development of allergic airway disease model in mice HAN Ling

作　　者：韩灵[1] 孙悦奇[2] 付清玲[1] 文卫平[1] 史剑波[1] 

机构地区：[1]中山大学附属第一医院耳鼻咽喉科医院,广州510080 [2]暨南大学第二临床学院

出　　处：《中华耳鼻咽喉头颈外科杂志》2013年第3期224-228,共5页Chinese Journal of Otorhinolaryngology Head and Neck Surgery

基　　金：国家自然科学基金（81170896、81271055）

摘　　要：目的探讨建立呼吸道变应性炎性反应小鼠模型的方法。方法采用卵清白蛋白（ovalbumin，OVA）作为变应原，对模型组（5只）BALB／c小鼠腹腔注射OVA与免疫佐剂（氢氧化铝）致敏，空气雾化吸入联合鼻腔滴注OVA试剂激发的方法构建模型。另设对照组（5只），用磷酸盐缓冲液（PBS）替代OVA进行致敏和激发。末次激发后对小鼠鼻部症状进行评分，评估小鼠鼻黏膜嗜酸粒细胞浸润、肺组织支气管周围炎性反应细胞浸润和支气管上皮杯状细胞增生等病理学改变情况，检测小鼠血浆OVA特异性IgE抗体浓度，检测小鼠肺泡灌洗液中自细胞介素（interleukin，IL）4和IL-5细胞因子水平。结果模型组小鼠能够成功模拟出打喷嚏、鼻痒挠鼻等症状，并且成功诱导出鼻中隔黏膜下嗜酸粒细胞及其他炎性反应细胞的浸润，肺部小支气管和小血管周围炎性反应细胞的浸润，以及支气管上皮杯状细胞的增生等病理生理学改变。模型组、对照组小鼠血浆OVA特异性IgE抗体质量浓度分别为（1237．00±153．20）、（191．904-43．20）og／ml；模型组、对照组小鼠肺泡灌洗液中IL-4分别为（46．50±10．15）、（7．96±1．80）pg／ml，IL-5分别为（50．81±11．41）、（7．53±2．23）pg／ml，两组差异均有统计学意义（t值分别为6．569、3．738、3．724，P值均〈0．05）。结论采用OVA致敏和激发的造模方案，建立一种同时了解上下呼吸道的变应性炎性反应的小鼠模型，为研究发病机制和药效评估提供了一种可行的研究方法。Objective To investigate the method of development of allergic airway disease model in mice. Methods Ten BALB/c mice were devided into the model group and the control group. Each group contained 5 mice. Ovalbumin （OVA） was used as allergen. OVA was emulsified with aluminum hydroxide and injected intraperitoneally for sensitization. Afterwards the mice from model group were challenged with aerosolized 5% OVA and subsequently instilled with OVA intranasally. For the blank control group the mice were sensitized and challenged with phosphate buffer saline （PBS）. After final challenge, the nasal symptoms were scored, and mice were sacrificed for evaluation of eosinophilia of nasal septum, peribronchial inflammation and goblet cell hyperplasia. Mice serum was collected for measurement of OVA-specific IgE concentration, and levels of IL-4 and IL-5 from bronchoalveolar fluids were also tested. Results Compared with blank control mice, mice from model group displayed typical sneezing and nasal scratching symptoms. The histopathological changes, such as eosinophilia of nasal septum mucosa, infiltration of peribronchial inflammatory cells and hyperplasia of goblet cells were successfully induced by OVA sensitization and challenge. Moreover, mice in model group showed higher level of OVA-specific IgE in serum and IL-4 and IL-5 cytokines in bronchoalveolar fluids [ mice from model group： IgE （1237. 00 ± 153.20） pg/ml, IL-4 （46. 50 ±10. 15） pg/ml, IL-5 （50. 81 ± 11.41 ） pg/ml; mice from control group： IgE （ 191.90 ±43.20） pg/ml, IL-4 （7.96 ±1.80） pg/ml, IL-5 （7.53 ±2.23） pg/ml;t value were 6.569, 3.738 and 3.724, respectively, all P 〈 0.05 ]. Conclusion The method using OVA as allergen could effectively develop a mouse model of allergic airway disease which could be used for pathogenesis study and drug effect evaluation.

关 键 词：疾病模型 动物 小鼠 呼吸超敏反应 卵白蛋白 

分 类 号：R-332[医药卫生]