| Objective:To observe the expression of MMP-8、MMP-9、MMP-12and TIMP-1、TIMP-4in the lung tissue of rats with COPD.To research the effect of MMP-8、MMP-9、MMP-12and TIMP-1、TIMP-4on the occurrence and developmentof COPD. To explore the effect and mechanism of hypo-lipidemic in COPD.Methods:1Preparation of COPD model:SD rats were randomly divided into three groups:control group, the smoke-exposed group and the simvastatin group. In addition to the control group, the rats in other two groups were exposed to secondhand cigarette smoke in the fume box twice a day for4months. Simvastatin, at a dose of5mg/kg, was administered orally to rats in the simvastatin groups once per day for4months.The weight of rats was detected, the number and classification of WBC in bronchoalveolar lavage fluid (BALF) were determined, and pathological morphology of lung tissue was observed.2The expression of MMP-8、MMP-9、MMP-12and TIMP-1、TIMP-4proteins in rat lung tissue were detected with immunohistochemistry.The expression of MMP-8、MMP-9、MMP-12mRNAs and TIMP-1TIMP-4mRNAs in rat lung tissue was measured by real-time quantitative PCR.Results:1The percentage of neutrophils, macrophagocytes and total white blood cells in BALF of rats in smoke-exposed group were higher than those in control group (P<0.01). The mean lining interval (MLI) and bronchial wall thickness/diameter were significantly increased (P<0.01), and the mean alveolar number (MAN) was significantly decreased (P<0.01). Compared with smoke-exposed group, simvastatin had no significant effects on percentage of cells in each category, MAN, MLI and bronchial wall thickness/diameter (P>0.05).2Compared with control group, the protein expression of MMP-8、MMP-9、 MMP-12was significantly increased in smoke-exposed group by the way of immunohistochemistry. The expression of TIMP-1、TIMP-4protein was increased too. Compared with the smoke-exposed group,the expression of TIMP-1、TIMP-4protein in simvastatin group was increased, but the expression of MMP-8、MMP-9、MMP-12protein was decreased.3Compared with control group, the mRNA expression of TIMP-1and TIMP-4was increased in smoke-exposed group by the way of real-time quantitative RT-PCR.(P<0.01). The mRNA expression of TIMP-1and TIMP-4in rat lung tissue in smoke-exposed group was (5.18±1.44) times and (2.58±0.42) times than that of control group. Compared with smoke-exposed group, the mRNA expression of TIMP-1and TIMP-4was increased in simvastatin group. The mRNA expression of TIMP-1and TIMP-4in rat lung tissue in simvastatin group was (6.71±2.60) times and (3.61±0.38) times of that in control group. The mRNA expression of MMP-8、MMP-9and MMP-12was significantly increased(P<0.01). The mRNA expression of MMP-8、MMP-9and MMP-12in rat lung tissue in smoke-exposed group was respectively (7.71±0.87) times、(8.02±3.43) times and (6.89±2.53) times of that in control group. Compared with smoke-exposed group, mRNAs expression of MMP-8、MMP-9and MMP-12was decreased in simvastatin group respectively (P<0.05, P<0.05, P>0.05). The mRNAs expression of MMP-8、MMP-9and MMP-12in rat lung tissue in simvastatin group was respectively (3.62±2.20) times,(3.37±0.26) times and (2.74±0.90) times of that in control group. Conclusion:1In my study, COPD rat model was successfully established by inhalation of cigarette smoke for four months. The number of WBC and the classification in BALF was decreased by simvastatin treatment, but there was no significant change on pathological morphology of rat lung.2MMP-8、MMP-9、MM-12and TIMP-1、TIMP-4play important roles in the appearance and improvement of COPD. Simvaastatin treatment could improve the imbalance of MMPs and TIMPs, and that might be a new target for prevention and treatment of COPD. |
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