构建大鼠慢性阻塞性肺疾病合并肺间质纤维化的模型  

The model of chronic obstructive pulmonary disease combined with interstitial pulmonary fibrosis induced by cigarettes and LPS in rats

作　　者：郭丽萍[1] 司靓[1] 吴雅丽[1] 丁立君[1] 宋贝贝[1] 阎锡新[1] 

机构地区：[1]河北医科大学第二医院呼吸内科,河北石家庄050000

出　　处：《中国现代医学杂志》2009年第11期1601-1604,1608,共5页China Journal of Modern Medicine

摘　　要：目的慢性阻塞性肺疾病(COPD)合并肺间质纤维化是COPD进展的必然趋势和病理结局,但其潜在机理尚未阐明,通过成功复制此动物模型来探讨COPD合并肺纤维化的可能发病机制,为临床提供预防、诊断及抗炎、抗纤维化治疗的新思路。方法雄性SD大鼠随机分成正常对照组(A组)、28d模型组(B组)、42d模型组(C组),在不同时间处死,进行支气管肺泡灌洗液(BALF)炎性细胞计数和分类;观察肺组织的病理形态学改变;肺功能变化;免疫组化方法测定肺组织中的胶原蛋白III阳性面积比;血清和BALF转化生长因子-β(1TGF-β1)含量变化。结果造模4周,动物模型出现慢性支气管炎性和肺气肿的表现,6周后出现纤维化表现;BALF中细胞总数:B组和C组细胞总数较对照组有明显升高(P<0.01);BALF中炎性细胞分类:B组中性粒细胞数%(PMN%)较对照组有明显升高(P<0.01),C组淋巴细胞数%较对照组有明显增高(P<0.01);肺功能变化:B组和C组0.3s用力呼气容积占用力肺活量比(FEV0.3/FVC)、呼气峰值流速(PEF)、呼气中期流速(MMF)较正常对照组降低(P<0.05),C组PEF、MMF较B组降低(P<0.05);肺组织胶原蛋白Ⅲ含量高于正常对照组,两组比较差异均有显著性(P<0.01);血清和BALF中,B组和C组TGF-β1含量均高于正常对照组,但无统计学意义(P>0.05)。结论该实验所制备的模型符合人类慢性阻塞性肺疾病合并肺间质纤维化的病理特点。[Objectives] The chronic obstructive pulmonary disease combined with interstitial pulmonary fibrosis （IPF-COPD） is an inevitable trend and pathological outcome of the chronic obstructive pulmonary disease, but its mechanism has not been illuminated. The possible mechanism of IPF-COPD would be explored by replicating animal models. This study aimed to provide the new idea about its prevention, diagnosis and the therapy of anti-inflammatory and anti-fibrosis of IPF-COPD for clinical practices. [Methods] The male SD rats were devided into three groups randomly： group A was normal control group, group B and group C were model group 28 days and 42 days respectly.The rats would be executed at different time. Bronchoalveolar lavage fluid （BALF）would be collected for counting the total leukocytes and categorization. The changes of pathomorphism of lung were observed by HE, Masson, and the content of collagen protein Ⅲ were determined by immunohistochemistry. The pulmonary function of the rats was investigated. [Results] Chronic bronchitis and emphysema were appeared in model B and pulmonary fibrosis was appear in group C. The total leukocytes in group B were higher than those of control group （P 〈0.01）. Comparing to control group, the percentage of lymphocyte in group C was higher than control group. Changes of pulmonary function：FEV0.3/FVC, PEF, MMF were lower in group B and C compard with group control （P 〈0.05）. The content of collagen protein Ⅲ in lung of rats in group B and C were increased significantly than control group （P 〈 0.01）. [Conclusionsl The animal model in this experiment is consistent with the pathological characters of chronic obstructive pulmonary disease combined with interstitial pulmonary fibrosis in human.

关 键 词：慢性阻塞性肺病合并肺间质纤维化 吸烟 脂多糖 转化生长因子-Β1 

分 类 号：R-332[医药卫生] R563