应用熏烟联合脂多糖方法建立慢性阻塞性肺疾病相关肺动脉高压小鼠模型  

Cigarette smoking plus airway LPS inhalation induced COPD-PAH in mouse

作　　者：李征途[1] 徐小明[1] 巩雪芳[1] 张科东[1] 张晨婷[1] 姜华[1] 陈豫钦[1] 王胜[1] 卢文菊[1] 王健[1] 

机构地区：[1]广州医学院第一附属医院呼吸疾病国家重点实验室,510120

出　　处：《国际呼吸杂志》2014年第1期27-30,F0003,共5页International Journal of Respiration

基　　金：国家自然科学基金（81170052）;教育部长江创新团队项目（IRT0961）;广东省自然科学基金团队项目（1035101200300000）;广东省科技攻关项目（20108031600301）

摘　　要：目的建立一种慢性阻塞性肺疾病相关肺动脉高压（COPD—PAH）小鼠模型。方法模型组小鼠第1天和第14天鼻内滴注脂多糖（LPS），其余时间每天熏烟4h，上下午各2h，10支香烟／h，6d／周，持续熏烟3个月。对照组小鼠不做任何干预。建模期间监测小鼠体质量变化。建模结束后，检测以下指标：肺功能和右心压力；小鼠支气管肺泡灌洗液中炎症细胞总数和细胞类型；用EI，ISA方法检测肺组织中细胞因子KC和黏蛋白MucSac的水平。并观察气道和肺组织病理改变。结果与对照组相比，模型组小鼠体质量和动态肺顺应性显著降低，吸气阻力、右心室平均压和右心室重量／体质量比等显著增加。模型小鼠支气管肺泡灌洗液中自细胞总数升高，以巨噬细胞为主，并伴随中性粒细胞明显增加。肺组织KC和Muc5ac蛋白均较对照组明显增多。肺组织切片PAS染色显示模型组杯状细胞增生。此外，在模型组小鼠肺切片中观察到炎症浸润，气管壁和肺小血管壁平滑肌增厚，气管基底层下胶原沉积，提示气管和肺血管重塑的发生。结论用这种熏烟结合气道内滴注LPS的方法可以在短期内建立COPD-PAH小鼠模型。Objective To establish a COPD^PAH mouse model induced by cigarette smoking exposure plus airway LPS inhalation. Methods Model mice were given LPS by intranasal inhalation on day 1 and day 14. The cigarette smoking exposure was carried out by two hours per time, twice every day, and 6 days per week in a dose of 10 pieces of cigarettes per hour within three months. Control mice didnrt receive any treatment. The mice body weights were monitored during the process. The model establishment was evaluated according the following parameters： the lung function and right heart pressure; the total and differential cell numbers in bronchial alveolar lavage fluid （BALF） ;the KC protein and mucin MucSac levels in lung by ELISA; and the pathological changes on lung tissue. Results Compared with the control mice, the body weights and dynamic lung compliance were significantly reduced, the RI, right ventricular average pressure, right ventricular weight/body weight ratio, the total cells in BALF in which major cells were macrophages with augmented neutrophils, and the levels of lung KC and Muc5ac protein were significantly increased in model mice. The histological staining showed that goblet cell hyperplasia, lung inflammation, the thickening of smooth muscle layer on bronchia and lung small vessel and subepithelial collagen deposition occurred in model mice, which indicated the ongoing lung remodeling. Conclusions C{）P[〉PAH mouse mode was established by cigarette smoking exposure plus airway LPS inhalation. This model can be used to study the effects of bacterial infection on COPD- PAH progress.

关 键 词：熏烟 脂多糖 慢性阻塞性肺疾病相关肺动脉高压小鼠模型 

分 类 号：R563.9[医药卫生—呼吸系统] R-332[医药卫生—内科学]