The Expression Of ICAM-1,MMP-9 In COPD Model Rats And The Effection Of Erythromycin On It

Objective:By smoking as well as endotracheal injection of lipopolysaccharide(LPS) we established COPD rat models,to explore the role of ICAM-1 and MMP-9 in the pathogenesis of COPD,and to study the effects of erythromycin(EM) on lung ICAM-1 and MMP-9 expression in vivo experiment of COPD rats,and developing the anti-inflammtion effects of EM in COPD.Methods:36 male Wistar rats were randomly divided into three groups:The COPD model group,The EM intervention group and The control group.The COPD model group was established by endotracheal injection of 200ug LPS on the first and fourteenth day,passive smoking was given for 0.5h/d for one month,and normal saline solution gavage 2ml from the 15th day.The EM intervention group was treated with EM gavage at a dose of 100mg/kg just before exposure to cigarette smoke everyday from the 15th day,modeling method was same with COPD group.The control group was given no passive smoking and normal saline solution on the first and fourteenth day instead of LPS,normal saline solution gavage 2ml everyday from the 15th day.Lung function tests were performed one month later and we tested FEV_0.3/FVC,R1 and Cdyn.BALF were collected to count the total and differential cell counts.The pathological change were observed.Expressions of ICAM-1 and MMP-9 were detected by immunohistochemistry.Correlation of data in COPD group were analyzed.Results:(1) COPD and intervention rats gradually emerged diet and activity decreaing,the average body weight mitigated compared with the control group,in the later period appearing dry and yellow hair and the sound of gasping could be heard,the normal group was out of this situation.(2) Lung function tests showed that FEV_0.3/FVC and Cdyn were significantly lower in the COPD group and EM intervention group than in the control group(both P＜0.05),R1 was higher in the COPD group and EM intervention group than in the control group(both P＜0.05);compared to the COPD group,FEV_0.3/FVC and Cdyn were significantly increased (P＜0.05),R1 decreased significantly in EM intervention group(P＜0.05). (3) WBC counts,PMN counts and AM counts in BALF of COPD and EM intervention group were significantly increased than those of control group(both P＜0.05);compared to COPD group,WBC counts,PMN and AM counts counts in BALF of EM intervention group decreased remarkably(both P＜0.05);(4) The pathologic change of chronic bronchitis and obstructive emphysema were observed in lung tissue of The COPD group and EM intervention group,and the pathological changes of EM intervention group were lighter remarkably than COPD group.(5)Compared to the control group,the expression of ICAM-1 and MMP-9 in COPD group and EM intervention group were significantly increased(both P＜0.05);the expression of ICAM-1 and MMP-9 in EM intervention group were significantly lower than that of The COPD group(P＜0.05).(6) Correlations analyze in COPD group:Negative correlations were demonstrated between WBC counts,PMN counts AM counts and FEV_0.3/FVC(r=-0.61,P＜0.05;r=-0.80,P＜0.01;r= -0.67,P＜0.05 respectively);Positive correlations were demonstrated between the expression of ICAM-1 and WBC counts,PMN counts (r=0.83,P＜0.01;r=0.68,P＜0.05 respectively);Positive correlations were demonstrated between the expression of MMP-9 and WBC counts,PMN counts(r=0.62,P＜0.05;r=0.60,P＜0.05 respectively);Negative correlations were demonstrated between the expression of ICAM-1,MMP-9 and FEV0.3/FVC(r=-0.70,P＜0.01;r=-0.71,P＜0.05 respectively); Positive correlations were demonstrated between the expression of ICAM-1 and MMP-9(r=0.71,P＜0.01)Conclusion:(1) The rat model of COPD established by passive smoking for one month and endotracheal injection of LPS twice is successful(2) The difference of expression of ICAM-1 and MMP-9 between COPD group and control group have statistical significance, which indicate that ICAM-1 and MMP-9 may play important role in the formation of COPD.(3) EM may play a certain protective role in the treatment of COPD through decreasing the expression of ICAM-1 and MMP-9 and weakening the inflammatory response.