The Expression Of Matrix Metalloproteinases-9(MMP-9) And His Tissue Inhibitor (TIMP-1) In The Lung Of Smoke-induced COPD In Rats

【OBJECTIVE】To investigate the expression of matrix metalloproteinases-9(MMP-9)and his tissue inhibitor (TIMP-1) in the lung of smoke-induced chronic obstructivepulmonary disease(COPD) in rats and the therapeutic effect of pulmonary surfactant.【METHODS】COPD animal model was established by smoke inhalations andintratracheal instillations of lipopolysaccharide in Wistar rats. Thirty Wistar ratswere randomly divided into 3 groups as follows: normal group(N), controlgroup(C),and treatment group(T).The last two groups received smoke inhalationsdaily for 6 weeks and received intratracheal instillations of lipopolysaccharide twice,one of which received exogenous pulmonary surfactant treatment(100mg/Kg BW) inthe 2nd,3rd,5th,6th week(4 times) by intratracheal instillation before exposure tocigarette smoking. Lung function test,blood gas analysis,light microscopyobservations were performed in each group. Pulmonary mean linear intercept (MLI),mean alveolar numbers (MAN), and pulmonary alveolar area (PAA) was measured byimage analysis. The expression of MMP-9 and TIMP-1 were observed byimmunohistochemistry.【RESULTS】Smoking for 6 weeks and instillations of lipopolysaccharide twiceresulted in chronic bronchitis and emphysema(Fig 2,5). MLI and PAA increased andMAN decreased in the two experimental groups compared with in the normal group(P＜0.01)(table 1).FEV_0.3 and FEV_0.3/FVC decreased and Re increased in the twoexperiment groups compared with in the normal group (P＜0.01)(table 2).PaO₂decreased and PaCO₂ increased in the two experimental groups compared with in thenormal group(table 3). Administration of exogenous pulmonary surfactant for 4times resulted in statistically significant inhibition of pulmonary injury (Fig 3, 6).MLI and PAA decreased and MAN increased in T compared with in C(P＜0.01).Thelung function was improved in T compared with in C(P＜0.01): FEV_0.3 andFEV_0.3/FVC increased and Re decreased in T, also the PaO₂ increased and PaCO₂decreased. The expresstion of MMP-9 increased significantly (P＜0.01) and the ratioMMP-9/TIMP-1 was unbalance in model group (Fig8,11) with N(Fig7,10).Administration of exogenous pulmonary surfactant for 4 times resulted in statisticallysignificant inhibition of pulmonary injury. The expression of MMP-9 was reduced(P＜0.01)and the ratio MMP-9/TIMP-1 was regulated to balance in control group with C.【CONCLUSION】pulmonary surfactant may down-regulate the expression ofMMP-9 and modulate the equilibration of the ratio of MMP-9/TIMP-1,supressinflammatory reaction ,protect pulmonary and delay progress in COPD.pulmonary surfactant may have a protective and therapeutic effect on COPDmodel of rats by alleviating airway inflammatory reaction, decreasing the destructionof alveolar and improving the lung function.