[The role of matrix metalloproteinases in extracellular matrix remodelling in chronic obstructive pulmonary disease rat models].
摘要
OBJECTIVE: To study the role of metalloproteinases(MMPs) in the airway extracellular matrix (ECM) remodelling of chronic obstructive pulmonary disease (COPD) rat models. METHODS: The COPD rat models which was established by intratracheal instillation of 200 microg lipopolysaccharide once for every two weeks(twice), and exposed to 5% smoke for 0.5 h/d for 4 weeks. The pathological changes were observed, lung function and blood gas changes were also deter mined. The fibroblasts, lymphocytes of bronchial walls and alveolar macrophages were counted. The hydroxyproline of bronchial lung tissue homogenates were deter mined by biochemistry method. The expression of MMP-9,MMP-2 and tissue inhibitor of metalloproteinase-1(TIMP-1) in bronchi and lung tissue was verfied by immunohistochemical analysis and by reverse transcription-polymerase chain reaction analysis. The gelatinolytic activities of MMPs of lung tissue were performed by gelatin zymographic analysis. RESULTS: The pathological changes of bronchi and lung tissue, the changes of lung function and blood gas analysis were similar to those of the COPD patients. The number of fibroblasts, lymphocytes and alveolar macrophages of model group were significantly increased than those of control group (P < 0.001). The hydroxyproline of model group was significantly in creased than that of control group (P < 0.001). By using image analyzer, immunoreactivity of MMP-9, MMP-2,TIMP-1 were markedly increased in epithelial cells of bronchi, fibroblasts, macrophages, endothelial cells and pneumocytes in model group as compared with those of control group. The protein expressions of MMP-9, MMP-2 and TIMP-1 in model group were significantly increased than those in control group(P < 0.0001 or P < 0.01). The mRNA expression of MMP-2, MMP-9 and TIMP-1 in COPD model group (1.11 +/- 0.06,1.04 +/- 0.26 and 0.85 +/- 0.34,respectively) were significantly increased than those in control group (0.30 +/- 0.17,0.36 +/- 0.09 and 0.23 +/- 0.08,respec