慢性阻塞性肺疾病大鼠模型气道炎症与重塑的实验研究

目的：动态观察及评价慢性阻塞性肺疾病（COPD）大鼠模型的气道炎症及重塑的特点.方法：雄性Wistar大鼠,随机分为正常组、模型组,在不同时间点分批处死,进行肺泡灌洗液（BALF）中炎细胞计数和分类;观察肺组织的病理形态学改变;半定量图像分析法测量小气道管壁和平滑肌层厚度.结果：（1）造模第20d左右,动物模型出现慢性支气管炎和肺气肿的病理形态学改变,第20～40d期间炎症反应最重,第40d之后炎症反应呈慢性过程.（2）模型组管壁及平滑肌层均较正常对照组显著增厚（P＜0.01）,模型组小气道管壁厚度与平滑肌层厚度成显著正相关（r=0.87813,P＜0.01）.（3）BALF中炎细胞总数：M20、M30组较正常对照组显著增多（P＜0.01,P＜0.01）;BALF中炎细胞分类：M20组中性粒细胞比例较正常对照组显著增高（P＜0.01）,巨噬细胞比例显著下降（P＜0.01）.结论：本实验所制备的COPD大鼠模型符合人类COPD的病理形态学特点.慢性气道炎症的发复刺激引起管壁纤维性增生增厚及平滑肌层增厚,即气道重塑,最终导致气流受限.

The experimental study of the airway inflammation and remodeling of COPD rat model

Objective:To observe dynamically and evaluate the histopathological features of airway inflammation and remodling of COPD rat model.Methods:Male Wistar rats were randomly divided into:the health control group and the model group.Executed the rats at different time respectively,to observe the total and differential cell counts in bronchoalveolar lavage fluid(BALF)and the histopathological features;to measure the thickness of the airway wall and the smooth muscle layer of the small airway by means of image analyzer.Results:(1)At about the 20th day,the model group got the histopathological changes of chronic bronchitis and emphysema;from the 20th day to the 40th day,the inflammation was deteriorating;after the 40th day,the inflammation became chronic.(2)in the model group the thicknesses of airway wall and smooth muscle layer were significantly increased compared to the health control grouprespectivel(P<0.01).In model group the thickness of airway wall was positively correlated with that of smooth muscle layer(r=0.87813,P<0.01).(3)the total inflammatory cells of M20?M30 in BALF increased(P<0.01),while the macrophages was significantly decreased compared to the health control group(P<0.01).Conclusion:The pathological features of the COPD rat model was accorded with that of the human COPD.The stimulation of chronic inflammation caused the proliferation of fibroblasts and smooth muscle in the bronchioles which is called airway remodeling,and finally induced airflow obstruction.