反复铜绿假单胞菌感染诱导大鼠慢性阻塞性肺疾病模型探讨

Induction of rat model of chronic obstructive pulmonary disease by repeated infection with Pseudomonas aeruginosa

目的探讨反复铜绿假单胞菌(PA)感染能否诱导大鼠产生慢性阻塞性肺疾病(COPD)的病理生理及病理学改变。方法将120只Wistar大鼠随机分为铜绿假单胞菌感染组(PA组)和对照组(NS组)。PA组通过气管穿刺,多次注入一定剂量铜绿假单胞菌菌液,建立大鼠慢性肺部感染模型,测定大鼠动脉血气,观察肺组织病理改变,测量气管壁厚度和血管壁厚度。结果自感染第4周开始,PA组大鼠体重较NS组显著减轻(P<0.05);自第12周开始,PA组大鼠血气PaO2显著低于NS组(0.01<P<0.05),而PaCO2明显升高(0.01<P<0.05);从第2周开始,PA组大鼠气管壁厚度显著大于NS组(P<0.05);从第4周开始,PA组大鼠血管壁厚度显著大于NS组(P<0.05);至第16周,PA组大鼠各级支气管慢性炎症明显,管壁增厚,管腔明显狭窄,有气道重构和肺气肿形成。结论反复气道感染铜绿假单胞菌可致大鼠产生COPD的病理生理及病理学改变,具有COPD的主要特征,提示该方法可能为COPD大鼠模型的建立提供一条新的途径。

Objective To investigate if pathological and pathophysiological manifestation of a rat model of chronic obstractive pulmonary disease（COPD） can be induced by repeated infection with pseudomonas aeruginosa（PA）.Methods One hundred and twenty Wistar rats were randomly divided into PA group and control group（60 rats in each group）.Suspension of Pseudomonas aeruginosa（0.7×108 CFU/mL） was repeatedly injected into the trachea through puncture,on d1 and d4 per week for 4 weeks,and once in the next 4 weeks.At 8 weeks after the experiment,the body weight,blood gas analysis,pathologic changes in the lung tissue and the thickness of trachea wall and vessel wall in the rats of the two groups were determined.Results The body weight of PA group rats was significantly lower since the 4th week（P0.05）.From the 12th week,PO2 of PA group rats was significantly lower（0.01P0.05） than that of the NS group.On the contrary,PCO2 was significantly higher（0.01P0.05）.The small pulmonary vessels in the PA group rats were more thicker than that of the NS group from the 4th week（P0.05）,along with a gradually increased thickness of trachea wall from the 2nd week（P0.05）.At the 16th week,there appeared distinct chronic inflammation in all grade bronchi,while the bronchial wall was thickened and the bronchial lumen was narrowed.In addition,airway remodeling and emphysema also occurrred.Conclusions A rat model of COPD with its pathological and pathophysiological manifestation has been successfully induced by repeated infection with pseudomonas aeruginosa.It provides a new method in establishment of COPD animal models.