目的：确定慢性阻塞性肺疾病合并肺间质纤维化（PIF-COPD）的动物模型及检测指标。方法：大鼠气管滴入博来霉素（BLM）叠加香烟烟雾刺激构建PIF-COPD 动物模型。气管滴入6 mg·kg-1 BLM 并香烟烟雾刺激47 天，检测肺功能，计算肺指数，HE 染色观察肺组织病理形态学改变，天狼星红染色观察胶原I 和III 变化，用抗体微阵列蛋白质芯片检测血清细胞因子表达谱。结果：呼吸功能检测表明，与对照组相比，模型组大鼠的中心气道阻力、组织阻尼、动态弹性显著升高而动态顺应性显著降低，模型动物肺指数显著增加（P<0.01）；病理检测显示：模型动物肺组织表现为炎性浸润，I、III 型胶原含量明显升高，出现肺气肿、纤维化病理表现。模型组大鼠血清MMP-8 、TIMP-1、 IL-10、IL-13、 PDGF-AA 和Beta-NGF 较正常组增加明显，RAGE 较正常组减少。结论：大鼠6 mg·kg-1 BLM 气管滴入合并香烟烟雾刺激47 天，可作为PIF-COPD 的动物模型；模型组大鼠呼吸功能的检测、血清MMP-8、TIMP-1、IL-13、PDGF 和NGF 可作为该模型的评价指标。

This study was aimed to confirm animal model and evaluating indicators of the chronic obstructive pulmonary disease combined with pulmonary interstitial fibrosis (PIF-COPD). PIF-COPD rats were induced by intratracheal administration of Bleomycin(BLM, 6 mg·kg-1) and cigarette smoke stimulation for 47 days. After that,the lung function and index were measured. Changes of pathomorphism of lung were observed with hematoxylineosin staining. Collagen protein I and III were determined by Sirius red staining. The protein antibody microarray chip was employed for serum cytokine expression pattern measurement. The results showed that in the lung function testing, the central airway resistance, tissue damping, dynamic elasticity of model rats increased significantly and the dynamic compliance reduced significantly. The lung index of model rats increased significantly (compared with the control group, P < 0.01). The pathological tests showed that lung tissues of model rats showed emphysema and fibration with inflammatory infiltration, and content of collagen type I and III increasing significantly. The contents of MMP -8, TIMP -1, IL -10, IL -13, PDGF -AA, Beta -NGF of model rats serum increased obviously compared with the control group and RAGE reduced compared with the normal control. It was concluded that rats which were induced by intratracheal administration of BLM (6 mg·kg-1) and cigarette smoke stimulation for 47 days can be used as animal model establishment of PIF-COPD. The respiratory function and serum levels of MMP-8, TIMP-1, IL-13, PDGF and NGF can be used as evaluating indicators of PIF-COPD model.

北京中医药大学科研创新团队项目（2011-CXTD-12）：中药复方药物动力学研究创新团队，负责人：石任兵。