The Effect Of Erythromycin On Transforming Growth Factor-β₁ And γ-Glutamylcysteine Synthetase Of Lung In Smoking Rat

Objective:To explore the antioxidate therapeutic effect and the mechanisms of erythromycin for the treatment of chronic obstructive pulmonary disease,by observing the change of the pathologic,expiratory airway resistance and lung compliance and by determining the expression of transforming growth factor-β₁(TGF-β₁)andγ-glutamylcysteine synthetase(γ-GCS)in airway epithelial cells and alveolar macrophage of smoking rats treated by erythromycin,.Methods:Grade two male Wistar rats(n=30),weighted(150±10)g,were randomly divided into three groups:control group,smoking group and erythromycin group.Smoking group and erythromycin group were exposed to smoke for 4 hours separated twice one day,six days per week for twelve weeks.After smoking 4 weeks,erythromycin group were dosaged erythromycin intragastric administration 100mg/kg per day before smoking.The rest two groups were administered purified water,continuously 8 weeks.Then all rats were anesthetized with ethylcarbamate and measured expiratory airway resistance and lung compliance using Maclab data recorder analytical system,then determined the expression level of TGF-β₁ andγ-GCS proteinum(and their mRNA)in airway endothelial cell and alveolar macrophage respectively employing immunohistochemical method,immunocytochemical method and in-situ hybridization,moreover analysed the correlate relationship between them.Results:1.In comparison with control group,there was prominent emphysema change in smoking rats, the change was obviously relieve in erythromycin group.2.The expiratory airway resistance was increased and the lung compliance was degraded significantly in smoking group(0.567±0.032)cmH₂O/ml.s^-1,(0.414±0.018)ml/cmH₂O and erythromycin group(0.439±0.040)cmH₂O/ml.s^-1,(0.499±0.063)ml/cmH₂O in contrast with control group(0.274±0.021)cmH₂O/ml.s^-1,(0.603±0.047)ml/cmH₂O(P＜0.01),the airway resistance was lower(P＜0.01)and the lung compliance was higher(P＜0.05)in erythromycin group than that in smoking group.3.In contrast with control group(11.247±2.795),the expression level of TGF-β₁ proteinum in smoking(24.683±2.694)and erythromycin group(18.982±3.276)had obviously increased in airway endothelial cell(P＜0.01).After treatment with erythromycin,the proteinum level was significantly decreased(P＜0.01).The expression level ofγ-GCS proteinum in smoking group(24.967±2.886)and erythromycin group(18.473±2.697)was obviously increased in contrast with control group (13.289±1.471)in airway endothelial cell(P＜0.01).The proteinum level in erythromycin group was lower than that in smoking group(P＜0.01).4.In alveolar macrophage,the expression of TGF-β₁ and its mRNA in smoking group (23.883±2.842,16.290±2.531)and erythromycin group(17.166±2.946,11.469±2.763)were obviously higher than control group(11.914±2.455,8.664±2.142)(P＜0.05).Both the level of proteinum and its mRNA were obviously decreased after treated with erythromecin(P＜0.01). The expression ofγ-GCS proteinum and its mRNA in alveolar macrophage in smoking group(23.107±2.055,19.058±3.776)and erythromycin group(15.800±1.537,15.996±2.799) were obviously increased in comparison with control group(10.421±1.480,9.575±1.592) (P＜0.01).Both the level of proteinum(P＜0.01)and its mRNA(P＜0.05)in alveolar macrophage were lower in erythromecin group than that in smoking group.5.There was obviously positive correlation between TGF-β₁ andγ-GCS proteinum level in airway endothelial cell in smoking group(r=0.761,P＜0.05),but no correlations was found in erythromycin group.In alveolar macrophage,the proteinum(r=0.787,P＜0.01)and mRNA(r=0.887,P＜0.01)level ofγ-GCS were respectively positively correlated with the proteinum and mRNA expression of TGF-β₁ in smoking group.But above results were not found in erythromycin group.Moreover,the proteinum expression of TGF-β₁ andγ-GCS were respectively positively correlated with their mRNA level(r=0.910,r=0.867,P＜0.01).Conclusion:1.Erythromycin can improve pulmonary function and relief emphysema change induced by smoking on rats.2.The expressioin TGF-β₁ andγ-GCS are decreased in alveolar macrophage and airway endothelial cell after treatment with erythromycin,suggesting that erythromycin may play a certainly role in the antioxidate therapeutic in COPD.