内毒素诱导致敏小鼠建立支气管哮喘动物模型的实验研究  

Reproduction of asthma model in ovalbumin-sensitized mice by ovalbumin challenge and lipopolysaccharide induction

作　　者：顾鹏程[1] 许惠琴[1] 范欣生[2] 刘成鼎[1] 

机构地区：[1]南京中医药大学药理教研室,210029 [2]南京中医药大学江苏省方剂研究重点实验室

出　　处：《中华结核和呼吸杂志》2010年第1期56-59,共4页Chinese Journal of Tuberculosis and Respiratory Diseases

基　　金：国家“十一五”科技支撑计划资助项目（2006BAI06A02-01）

摘　　要：目的评价用内毒素（LPS）诱导卵清白蛋白（OVA）激发、OVA致敏的小鼠，建立支气管哮喘（简称哮喘）模型的方法。方法采用随机数字表法将120只BALB／c小鼠分为PBS对照组（A组，PBS致敏PBS激发）、OVA组（B组，OVA致敏OVA激发）、LPS／LPS小剂量组（C1组，50μg内毒素致敏50μg内毒素激发）、LPS／LPS大剂量组（C2组，100μg内毒素致敏100μg内毒素激发）、OVA／LPS小剂量组（D1组，OVA致敏、OVA雾化吸入激发结合50μg内毒素滴鼻诱导）、OVA／LPS大剂量组（D2组，OVA致敏、OVA雾化吸入激发结合100μg内毒素滴鼻诱导）。观察小鼠哮喘急性发作症状，检测BALF细胞分类计数，测定乙酰胆碱激发条件下气道反应性（以肺阻力RL表示）；HE染色观察肺组织病理变化。结果（1）D1组与D2组小鼠喘息症状加重，其中D2组更严重。（2）D1组与D2组BALF中细胞总数、巨噬细胞、淋巴细胞、嗜酸粒细胞、中性粒细胞均明显高于A组（均P〈0．05）。D1组的白细胞总数、淋巴细胞、嗜酸粒细胞、中性粒细胞均明显高于B组（均P〈0．01），D2组的白细胞总数、巨噬细胞、淋巴细胞、中性粒细胞均明显高于B组（均P〈0．05）。（3）以5g／L乙酰胆碱激发时，D1组RL[（9．32±1．51）cmH2O·ml^-1·s^-1（1cmH2O=0．098kPa）]和D2组RL[（44．21±2．88）cmH2O·ml^-1·s^-1]明显高于A组RL[（2．41±0．35）cmH2O·ml^-1·s^-1]和B组RL[（5．96±1．83）cmH2O·ml^-1·s^-1]，均P〈0．01。（4）D1组与D2组呈现较为严重的支气管哮喘病变，其中D2组病变程度明显加重。结论用内毒素诱导OVA致敏小鼠建立支气管哮喘模型的方法可产生更严重支气管炎症改变以及明显的气道高反应性。Objective To reproduce an asthma model in ovalbumin （OVA） -sensitized Balb/C mice by OVA challenge and Lipopolysaccharide （LPS） induction. Methods One hundred and twenty BALB/C mice were randomly divided into 6 groups： PBS control group （ A group, PBS sensitization and PBS challenge） , OVA group （ B group, OVA sensitization and OVA challenge）, low-dose LPS/LPS group （ C1 group, 50 μg LPS sensitization and 50 μg LPS challenge）, high-dose LPS/LPS group （ C2 group, 100 μg LPS sensitization and 100 μg LPS challenge） , low-dose OVA/LPS group （D1 group, OVA sensitization,OVA challenge and 50μg LPS induction ） and high-dose OVA/LIPS group （ D2 group, OVA sensitization. OVA challenge and 100 μg LPS induction ）. Asthmatic symptoms were observed. Airway responsiveness were assessed and lung resistance（ RL ）was calculated using a proprietary software program. Ceils in bronchoalveolar lavage fluid （BALF） were counted and lung histopathology was evaluated by HE staining. Results （ 1 ） Asthma symptoms in either D1 group or D2 group was more severe than other groups, especially in D2 group. （2） The level of total BALF ceils, macrophages, lymphocytes, eosinophils, and neutrophils in either D1 group or D2 group was significantly higher than that in A group （P 〈0. 05 ,P 〈0. 01 ）. The level of total BALF cells, lymphocytes, eosinophils, and neutrophils in D1 group was significantly higher than that in B group （P 〈 0. 01, respectively）. The level of total BALF cells, macrophages, lymphocytes, and neutrophils in D2 group was significantly higher than those in B group （P 〈 0. 05, respectively）. （3） When mice were stimulated by Ach （5.0 g/L）, RL in either D1 group [ （9. 32 ± 1.51 ） cm H2O · ml-^1 · s ^-1 （ 1 cm H2O = 0. 098 kPa） ] or D2 group [ （44. 21 ±2. 88 ）era H2O · ml^-1 · s^-1 ] was significantly higher than that in A group [ （2.41 ±0. 35） cm H2O · ml^-1 · s^-1] and B group [ （5.96 ± 1.83） cm H2O · ml^-1 · s^-1 ] �

关 键 词：内毒素类 哮喘 小鼠 

分 类 号：R562.25[医药卫生—呼吸系统] R773.9[医药卫生—内科学]