The Study Of Edaravone On Chronic Obstructive Pulmonary Disease Model Rats

Objective To discuss the effect of free radical scavenger edaravone in lung injuryof COPD rats and the possible mechanism.To develop the clinical application ofedaravone in COPD.Methods60healthy male SD rats was randomly diveded into six groups, namely,control group, COPD group, NAC group, edaravone low dose group(Eda1group),edaravone middle dose group(Eda2group) and edaravone high dose group(Eda3group), with10rats in each group, respectively. No intervention was applied in thecontrol group, COPD model was established by intratracheal instillation oflipopolysaccharide twice and exposure to cigarette smoke the other days.The rats inNAC group, Eda1group, Eda2group and Eda3group was intraperitoneal injected20mg/kg NAC,10mg/kgEda,20mg/kgEda,40mg/kgEda respectively before exposureto cigarette smoke. The lung function of rats was measured in Hsiang-Ya MedicalCollege, the level of MDA and SOD in plasma were measured by TBA and WST-1method respectively. The level of IL-8and TNF-α in BALF was measured by ELISA.The proteins of MMP-9MMP-12and TIMP-1in the lung tissue were detected byimmunohistoehemical method.Results1. In comparison with control group, f, RI was increased and Cdyn, PIFwas decreased in COPD group (p<0.05), NAC, middle and high dose edaravoneameliorated those changes (p<0.05).2. The plasma level of MDA in COPD group was significantly higher than those ofthe control group (p<0.05), NAC and edaravone, include low, middle and high dose,decreased plasma MDA level (p<0.05).3. Total white cell counts, neutrophil proportion and TNF-α level in BALF were higher in COPD group than those of the control group (p<0.05). Total white cellcounts was lower in NAC, middle and high dose edaravone group (p<0.05).Neutrophil proportion was lower in NAC and high dose edaravone group (p<0.05).TNF-α level was lower in every drug interfered group (p<0.05).4. In contrast with control group, COPD group showed the features of pulmonaryemphysema and inflammation. Those changes in NAC and high dose edaravonegroup were relieved. The MLI of the COPD group was significantly higher than thoseof the control group, while the MAN of the COPD group was significantly lower thanthose of the control group (p<0.05). Significant differences of MLI and MAN hadbeen found between the NAC, middle, high dose edaravone group and COPD group(p<0.05).5. The result of immunohistochemistry suggested that the expressions of MMP-9,MMP-12and TIMP-1in lung tissue of COPD group were higher than control group,moreover, the ratio between MMP-9, MMP-12and TIMP-1were also higher thancontrol group(p<0.05). NAC middle and high dose edaravone decreased theexpressions of MMP-9, MMP-12and TIMP-1in lung tissue and the ratio betweenMMP-9, MMP-12and TIMP-1(p<0.05).Conclusion NAC or edaravone could improve lung function, attenuate oxidativestress, inhibit the infiltration of inflammatory cells, restrain the release ofinflammatory factors, and decrease the secretion of matrix metalloproteinase. thus，edaravone can attenuate the development of COPD.