Effect Of Simvastatin On The Expression Of MMP-1、MMP-9 And TIMP-1 In Chronic Obstructive Pulmonary Disease Rats Serum And The Mechanism

Objective The aim is to establish the rat model of COPD and perform an intervention tosimvastatin by testing the situation of these enzymes in the lung tissue including MMP-1、MMP-9、TIMP-1, investigating the effect or possible mechanism simvastatin has on chronicobstructive pulmonary disease (COPD) influence and the possible mechanism in order toproviding experimental basis for its wide application in clinical treatment .Methods The method is to choose 30 male and clean wistar rats whose weight is (205±15)g , the group will be divided into three groups in a random way and there are ten wistar rats eachgroup .①The normal control group : feeding these normally for 40 days；②COPD model group:let the rats in the state of passive smoking for 38 days when preparing COPD model and dripLPS two times in the airway . Dripping 200μg / 200μl lipopolysaccharide (LPS) into theairways of the rats on the first day and on the fifteenth day , these rats are daily exposed to thesmoke in rest of the time；③The simvastatin treatment group: From the nine day during ratsare molding be given 5mg/kg simvastatin to fill the stomach , and the rest are exposed to thesmoke and drip LPS into the airways of the rats. After dyeing by HE , the pathology change oftheir lung tissue coming up can be observed through the light microscopy. Byimmunohistochemical method, we can test the expression level of MMP-1, MMP-9 and TIMP-1in the lung tissue of rat models .Results the general situation and the change of lung tissue pathology of Model rats arebasically common with the characteristics of chronic obstructive pulmonary disease which wehuman have. Compared with the control group, the expression level of MMP-1, MMP-9 andTMP-1 in the model group is significantly higher, the difference is statistically significant (P <0.05); among the three indexes of expression, the expression in the simvastatin treatmentgroup is obviously lower than the expression in the model group, the difference was statisticallysignificant (P < 0.05); the expression of MMP-1 / TIMP-1 and MMP-9 / TIMP-1 in the modelgroup is higher than these in the normal control group, the difference was statistically significant(P < 0.05), the expression in the Two groups of proportion in simvastatin treatment group isobviously lower than the expression of the model group, the difference was statisticallysignificant (P < 0.05).Conclusion（1）The animal models made by the method in which rats are given 38 days’passive smoking and dripped lipopolysaccharide (LPS) into the airway for two times isbasically common with pathology characteristics of human lung tissue .（2）The expression of MMP-1, MMP-9, TIMP-1, MMP-1 / TIMP-1, MMP-9 / TIMP-1COPD in the model group issignificantly higher than the expression of normal control group, and the difference wasstatistically significant, confirmed that the balance of the proportion of MMP-1, MMP-9,TIMP-1 and MMP-1 / TIMP-1, MMP-9 / TIMP-1 plays an important role in the COPDoccurrence, development process . (3) By reducing the expression of MMP-1、MMP、TIMP-1and balancing the proportion of MMP-1/TIMP-1、MMP-9/TIMP-1,simvastatin can inhibit theprocess of chronic inflammatory in airway, or lung tissue and lower the development trend ofCOPD , thus it will play a therapeutic effect.