熏香烟加气管注内毒素和单纯熏香烟法建立大鼠COPD模型  

Establishment of chronic obstructive pulmonary disease rat models by passive cigarette smoking and intratracheal instillation of lipopolysaccharide

作　　者：李红梅[1] 崔德健[1] 佟欣[1] 庞宝森[2] 高亚兵[3] 王德文[3] 

机构地区：[1]解放军304医院呼吸科,北京100037 [2]北京朝阳医院呼吸研究所,北京100020 [3]军事医学科学院病理室,北京100850

出　　处：《中国病理生理杂志》2002年第7期808-812,I002,共6页Chinese Journal of Pathophysiology

摘　　要：目的 :模拟人类吸烟及反复呼吸道感染可导致慢性阻塞性肺病 (COPD)的过程 ,采用熏香烟加气管注内毒素和单纯熏香烟法复制大鼠COPD模型 ,比较两种方法复制COPD模型的效果。方法 :4 8只Wistar大鼠随机分为①健康对照组 (对照I组饲养 4周 ;对照II组 ,饲养 3个月 ) ;②模型I组 :分别于第 (1、14 )d经气管注入内毒素2 0 0 μg,熏 5 %香烟 (第 1d、14d除外 ) ,0 5h/d ,共 2 8d ;③模型II组 :单纯熏 5 %香烟 0 5h/d ,共 3个月。测定各组肺功能及血气。HE染色及三联染色 ,并与COPD尸检支气管肺组织病理所见对比。生化法测定支气管肺组织羟脯氨酸含量 ,测量小支气管上皮层、固有膜层及平滑肌层截面积 ,支气管粘膜下层淋巴细胞及肺泡区巨噬细胞计数。结果 :病理观察示两模型组支气管肺组织病变与COPD患者尸检所见相符 ,但程度较轻。三联染色示两模型组气道壁胶原沉积显著多于对照组 ,模型II组较模型I组略少 ;两模型组上皮层及平滑肌层截面积显著大于对照组 (P <0 0 1或P <0 0 5 ) ,FEV0 3 /FVC %显著低于对照组 (P <0 0 1或P <0 0 5 ) ,模型I组吸气及呼气阻力显著高于对照组 (P <0 0 5 ) ,模型II组分钟通气量则显著低于对照组 (P <0 0 1) ;两模型组PaCO2 显著高于对照组 (P <0 0 1及P <0 0 5 ) ,模型I?AIM: To establish rat chronic obstructive pulmonary disease(COPD) models by passive cigarette smoking plus intratracheal instillation of lipopolysacchride(LPS) or passive cigarette smoking only, which would be similar to the pathogenesis of human COPD. METHODS: 48 Wistar rats were randomly divided into 4 groups.(1) Healthy control I group( n =12), rats were bred 4 weeks;healthy control II group( n =12), rats were bred for 3 months. (2) Model group I ( n =12), 200 μg lipopolysaccharide(LPS) was instilled intratracheally once for every two weeks and the rats were exposured to 5% of cigarette smoke, 0.5 h/d for 4 weeks.(3) Model group II(n=12),rats were exposed to 5% of cigarette smoke, 0.5 h/d for 3 months. The pathologic changes of airways and lung tissues, pulmonary function and blood gas analysis were determined. The airway wall lymphocytes and alveolar macrophages were counted. The cross areas of epithelial layer, smooth muscle layer and lamina propria of bronchi were measured. The hydroxyproline of lung tissue homogenates was determined by biochemistry method. RESULTS: The pathologic changes of airways and lung tissue of two models were similar to but milder than those of COPD patients(biopsy data). The collagen deposition and the cross areas of epithelial layer and smooth muscle layer in airway walls of two model groups were significantly increased than those of control groups( P< 0.01, P< 0.05).FEV 0.3 /FVC% of two model groups, PaO 2 and SaO 2 of model I group were significantly decreased, while R i and R e in model I group were significantly increased than that of control I group( P< 0.05). The PaCO 2 and the counts of lymphocytes and alveolar macrophages of both model groups were significantly increased than those of the control groups ( P< 0.01). Lots of alveolar macrophages had phagocyted smoke granules. The amounts of hydroxyproline of two model groups were significantly increased than those of control group(( P< 0.05) and were negatively related to the FEV 0.3 /FVC%,

关 键 词：COPD 烟雾 内毒素类 慢性阻塞性肺癌病 疾病模型 

分 类 号：R563[医药卫生—呼吸系统] R－332[医药卫生—内科学]