Abstract: Objective: To constract the mouse models of chronic obstructive pulmonary disease(COPD) induced by intranasal instillation of cigarette smoke extract(CSE) and lipopolysaccharide(LPS),and to explore its feasibility. Methods: Twenty-four C57BL/6J male mice were randomly divided into control group and model group, and there were 12 mice in each group. The COPD mouse model was established by intranasal instillation of CSE and LPS. The number of total cells,neutrophils and macrophages in bronchoalveolar lavage fluid(BALF) of the mice in two groups were determined,the pathological changes of lung tissue of the mice in two groups were observed, and the number of PAS positive cells,alveolar mean lining interval (MLI) and alveolar damage index (DI) (P<0.01)of the mice in two groups were determined.Western blotting method was used to detect the expression levels of E-cadherin, Vimentin, and α-SMA proteins in lung tissue of the mice in two groups. Results: The number of total cells,neutrophilis and macrophages in BALF of the mice in model group at 4 and 6 weeks of experiment was significantly higher than those in control group (P<0.01),and the typical mucus hypersecretion and emphysema in lung tissue of the mice in model group were found; the number of PAS positive cells, MLI(P<0.01),and DI(P<0.01) of the mice in model group at 4 and 6 weeks were higher than those in control group.Compared with control group,the expression level of E-cadherin protein in lung tissue of the mice in model group was decreased(P<0.01), and the expression levels of Vimentin and α-SMA proteins in lung tissue of the mice in model group were increased(P<0.01). Conclusion: The mouse model of COPD is successfully established by intranasal instillation of CSE and LPS in a short period of time.

Key words: chronic obstructive pulmonary disease, disease model,animal, cigarette smoke extract, lipopolysaccharide, bronchoalveolar lavage fluid