一种熏烟小鼠慢性阻塞性肺疾病模型的建立及鉴定  

Establishment of a cigarette smoke induced chronic obstructive pulmonary disease mouse model

作　　者：张科东[1] 马冉[1] 李征途[1] 徐小明[1] 张晨婷[1] 巩雪芳[1] 齐亚飞[1] 陈豫钦[1] 姜华[1] 郑则广[1] 王健[1] 钟南山[1] 卢文菊[1] 

机构地区：[1]广州医学院第一附属医院、广州呼吸疾病研究所呼吸疾病国家重点实验室,510120

出　　处：《国际呼吸杂志》2012年第21期1607-1611,共5页International Journal of Respiration

基　　金：国家教育部长江创新团队项目（20098050700041）;广东省自然科学基金团队项目（1035101200300000）资助

摘　　要：目的建立一种熏烟诱导的小鼠慢性阻塞性肺疾病（c0PD）模型。方法将小鼠随机分为COPD模型组和正常对照组，模型组小鼠每天熏烟两次，每次2h，每周熏烟6d，香烟剂量为9支／h。模型制备期间，每星期称量一次体质量，每个月检测一次小鼠肺功能。对照组小鼠不做任何干预。熏烟满6个月后，行肺功能检测，并检测小鼠支气管肺泡灌洗液（BALF）中炎症细胞数和黏蛋白MUC5AC水平，观察气道和肺组织病理改变等。结果与对照组相比，模型组小鼠体质量明显降低（P〈0．05），吸气阻力明显增加（P〈0．05），吸气峰流速、呼气峰流速和动态肺顺应性明显降低（P〈O．05）；肺泡灌洗液中白细胞总数，中性粒细胞、巨噬细胞和淋巴细胞分类计数与对照组相比，均明显增加；模型组小鼠肺切片HE染色显示炎症浸润，PAS染色显示气道上皮中出现大量黏液分化细胞，BALF中MUC5AC表达水平较正常组增加（P〈0．01）。结论用这种熏烟的方法所建立的小鼠COPD模型符合人类COPD的病理和功能改变，是建立小鼠COPD模型的理想方法。Objective To establish a cigarette smoke-induced chronic obstructive pulmonary disease （COPD） mouse model. Methods C57 mice were randomly divided into COPD model group and normal control group. The model group mice were exposed to cigarette smoke for twice per day,2 hours for each time with nine cigarettes per hour,6 days every week in 6 months. Control mice were exposed to room air only. During the six-month-exposure, both groups of mice were weighed every week and their pulmonary functions were measured once every month. Then the mice were dissected after the last pulmonary functions determination and the succeed of the model establishment was judged by evaluating the following parameters：the inflammatory cell numbers and mucin MUC5AC levels in hronchoalveolar lavage fluid （BALF）,the phenotypes on lung pathological changes, and the parameters of pulmonary functions. Results Compared with the normal control mice, the cigarette smoked mice have lower body weights （ P〈0.05）, enhanced inspiratory resistance （RI）, and decreases on peak inspiratory flow （PIF）, peak expiratory flow （PEF） and dynamic compliance （Cdyn） （P 〈0.05）. The total leucocyte numbers and the numbers of neutrophils, macrophages and lymphocytes in BALF were increased significantly in cigarette smoked mice which developed more severe lung inflammation and more mucus cells hyperplasia assessed by HE staining and PAS staining respectively. And higher levels of MUC5AC in BALF were found in cigarette smoked mice （ P 〈 0.01 vs control mice）. Conclusions The COPD mouse modelestablished with cigarette smoke mimics the clinical situations with similar pathological changes to the COPD patients and can be taken as an effective animal model for future COPD research.

关 键 词：熏烟 慢性阻塞性肺疾病模型 

分 类 号：R563.9[医药卫生—呼吸系统]