烟雾暴露所致肺气肿小鼠模型的建立与评价  

Establishment and Assessment of a Mouse Model of Cigarette Smoke-Induced Emphysema

作　　者：曹君[1] 陈平[1] 杨悦[1] 欧阳若芸[1] 彭红[1] 

机构地区：[1]中南大学湘雅二医院呼吸内科,长沙410011

出　　处：《中国实验动物学报》2010年第4期278-282,I0002,共6页Acta Laboratorium Animalis Scientia Sinica

基　　金：国家科学自然基金资助项目(编号:30770931;30800503);湖南省自然科学基金资助项目(编号:09JJ3036;07JJ3037)

摘　　要：目的探讨单纯烟雾暴露所致肺气肿小鼠模型建立及病理学、气道炎症及肺功能评价,并进行支气管肺泡灌洗(bronchoalveolar lavage,BAL)技术的改进。方法 20只C57BL/6J小鼠随机分为正常对照及烟雾暴露组,烟雾暴露90d并观察30d后行小鼠肺功能检查、应用改进方法留取BALF行细胞计数及行肺组织病理切片观察,并与正常对照组进行比较。结果烟雾暴露组小鼠气道阻力(Raw)较正常对照组增高,动态肺顺应性(Cdyn)降低;BALF中细胞总数高于正常对照组,巨噬细胞数(AM)、中性粒细胞数(N)、中性粒细胞所占比例(N%)也高于对照组,差异均有统计学意义;病理学观察示烟雾暴露组肺泡腔扩大、部分肺泡间隔断裂、肺泡腔融合、肺气肿形成,气道上皮排列紊乱、部分气道上皮增生、周围炎症细胞浸润并伴有平滑肌增生;形态学计量分析示烟雾暴露组平均内衬间隔(MLI)及肺泡破坏指数(DI)较正常对照组增加。应用改进技术行BAL成功率100%,回收率高达90%。结论单纯烟雾暴露可以成功建立小鼠肺气肿模型且稳定可靠,与人类慢性阻塞性肺病相似性好,经BAL技术改进后该模型可行性高。Objective To set and evaluate a mouse model of cigarette smoke（CS）-induced emphysema and improve the method of bronchoalveolar lavage（BAL）. Methods Adult （ n = 10,18 ～ 20 g body wt） male C57BL /6J mice （ CS-exposed group） were exposed 4 times per day,whole body,to CS from six cigarettes for consecutive 90 days and then to observe for another 30 days. The control group （n = 10） was sham-smoked. An improved method of bronchoalveolar lavage was used and the data of pulmonary function,bronchoalveolar lavage fluid （ BALF） and morphological manifestations were collected. Results Compared with the control group,the CS-exposed group owned higher airway resistance （ Raw）,lower dynamic lung compliance （ Cdyn）,more macrophages and neutrophils in BALF （ all P 0. 05）. Morphological detection showed significant enlarged airspace,disruption of alveolar septa and formation of emphysema. After using the improved method,success rate of BAL reached to 100% ,and recovery rate was up to 90% . Conclusion Cigarette smoke can induce emphysema stably in mice and this mouse model shows high similarity to human chronic obstructive pulmonary disease and is easy to manipulate after methodologic improvement.

关 键 词：慢性阻塞性肺疾病 肺气肿 香烟烟雾 动物模型 支气管肺泡灌洗 

分 类 号：R-563.3[医药卫生] R-332