The Effects Of Simvastatin On The Levels Of EMPs In Plasma Of COPD Rats

Objective: To observe the expressions of EMPs in plasma of COPD rats, and research the effects of simvastatin on the levels of EMPs, meanwhile investigate the possible mechanism of simvastatin in delaying the progression of COPD.Methods:1.thirty SD healthy male rats were divided into three groups at random(10 rats per group): normal control group,COPD group, simvastatin intervention group.2.To establish a COPD model,the rats were exposed in cigarette fumes 28 days, and injected LPS in trachea, on the 1st day and the 14 th day. Simvastatin(5mg/kg) were chronically administered to the intervention group rats once a day for 28 days, during cigarette exposure.Killing all the rats on the 30 th day,collect BALF to check the cell count and classify,observe the pathological changes of lung tissue and bronchus with HE staining under the microscope, and assessed the degree of rats' emphysema and the alveolar destruction by measuring the MLI and DI.3.The expressions of EMPs were analysed by flow cytometry(FCM).The degree of apoptotic pulmonary cells were observed by TUNEL assay. the expression levels of caspase-3 protease were observed by immunohistochemistry method.correlation analysis of the above results were compared too.Results:1. The pathological changes of lung tissue and bronchus in COPD set were highly conform to the changes of COPD.2.Cell count and classification of BALF: The proportion of neutrophils and the total number of cells in COPD group and intervention group were higher than the normal group(P<0.05),the consequences in intervention group were lower than COPD group(P<0.05),The proportion of macrophages in COPD set was deceased in comparison to the normal control group(P<0.05);The proportion in intervention group was higher than COPD group(P<0.05), The difference was statistically significant.3.MLI and DI:In comparison to the normal group, MLI and DI in COPD group and intervention group were increased(P<0.05,respectively);MLI and DI in intervention group, by contrast, were decreased in COPD group(P<0.05, respectively),The difference was statistically significant.4.The expression level of EMPs measured by FCM: compared with the normal group, the percentage of EMPs had a significant increase in COPD group and intervention group(P < 0.05),however the consequences of the intervention group had a decrease against to the COPD group(P<0.05), The difference was statistically significant. 5. The TUENL assay was used to detect the apoptosis of pulmonary cells, meanwhile measure the AI: The degree of pulmonary tissue cells' apoptosis in COPD group and intervention group had a significant stronger than the normal group(P<0.01), however compared with COPD group, the degree of cell apoptosis had a reduce in intervention group(P<0.01).6.The expression of caspase-3 protease which was detected by immunohistochemistry method and calculate IOD: the expression of caspase-3 protease in COPD group and intervention group had a significant increase than the normal group,and the intervention group's expression was weaker than COPD group; The IOD: IOD in COPD group and intervention group were increased against to the normalgroup(P < 0.01),In intervention group,IOD had a decrease in comparison to the COPD group(P<0.05). 7. The correlation analysis:the level of EMPs in rats' plasma and the value of N% in BALF, and AI in TUNEL, and IOD in caspase-3 had a significantly positive correction respectively(r=0.792,0.897,0.938;P <0.01,respectively).Conclusion:1.The expression level of EMPs increased in the plasma of COPD rats,it may be related to the apoptosis of lung vascular endothelial cells which induced by pulmonary inflammatory damage.2.Simvastatin reduced the lung tissue inflammatory and the expression level of EMPs and inhibited the lung tissue apoptosis.