The Effect Of Erythromycin On The Level Of MMP-9 In Rat Model Of COPD

Objective:The experiment observed the changes of lung MMP-9 expression level by erythromycin intervention in rat model of COPD.Our goal is to study and understand the effect of erythromycin on lung MMP-9 expression in vivo experiment of COPD rat,a further understanding of the anti-inflammatory effects of erythromycin,and developing the application of erythromycin in COPD.Methods:36 male rats were averagely divided into 3 groups in random.The COPD model group was established by the way of giving passive smoking for one month and endotracheal injection of LPS.Passive smoking was given once daily(0.5 hour)in a plexiglass box from the second day to the thirteen day and the fifteen day to the thirty day.In the first day and forteen day,LPS(200ug / 100ul)was given in trachea.The Erythromycin intervention group was treated with erythromycin gavage from the seventeenth day for 2 weeks,modelling method was the same with COPD group.The normal control was not given passive smoking. And in the first and forteen day,we gave each rat endotracheal injection of stroke-physiological saline solution instead of LPS.Lung function tests were performed for each rat one month later and we tested FEV0.3/FVC,Rl and Cdyn.Then the rat was put to death and the lung was taken out.Sections of paraffin-embedded left lungs tissue were cut, stained with HE,and processed for pathological observation. Immunohistochemistry was permormed for study the expression of MMP-9.The right lungs tissue was prepared for the examination of the expression of MMP-9 mRNA.Results:(1)COPD and Erythromycin intervention rats gradually emerged diet and activity decreasing,the average body weight mitigated compared with normal control group,in the later period appearing dry and yellow hair and the sound of gasping could be heard. The normal control group was out of this situation.(2)Lung function tests showed that FEV0.3/FVC,Rl and Cdyn values were significantly lower in the COPD and Erythromycin intervention groups than in the normal control group(P＜0.05).(3)The COPD and Erythromycin intervention groups lung tissue showed chronic obstructive bronchitis and emphysema pathological changes by light microscope.(4)Compared with the rats of normal control group,the expression MMP-9 protein increased significantly(P＜0.05)in the COPD rats.The positive coefficience of Erythromycin intervention group was lower than COPD group(P＜0.05).(5)In the COPD group MMP-9 mRNA in lungs increased significantly than normal control group(P＜0.05),the optical density ratio of Erythromycin intervention group was also lower than COPD group(P＜0.05).Conclusion:(1)The rat model of COPD which was established by the way of giving passive smoking for one month and endotracheal injection of LPS was successful,which was proofed by lung function tests and pathological observation.(2)MMP-9 levels in COPD rat lung tissue was significantly higher than normal rats,it plays an important role in the pathogenesis of COPD.(3)Erythromycin treatment of COPD rats reduced MMP-9 protein and mRNA expression levels can inhibit the migration of inflammatory cells and weaken inflammatory response.