Prophylactic effect of erythromycin on bleomycin-induced pulmonary fibrosis in rats

Objective To evalulate the effects and molecular mechanism of erythromycin (EM) in preventing experimental pulmonary fibrosis in rats.Methods Sixty healthy male SD rats were randomly divided into five groups:control group (group A),bleomycin group (group B),bleomycin and EM pretreatment group (group C),bleomycin and EM syntreatment group (group D),bleomycin and EM post-treatment group (group E).EM was administrated by oral at a dose of 100 mg/kg from day-3,0,7 to the rats respectively in the group C,D,and E.The equivalent volume of normal saline was administrated by oral to the rats in the group A and B.All experimental animals were sacrificed on day 14 and 28,six rats each time,a total of 30,and the lung specimens were harvested for Masson stain to observe pulmonary alveolitis and lung fibrosis.The content of hydroxyproline was measured by alkaline hydrolysis,While the expressions of protein and mRNA of transforming growth factor-β1 (TGF-β1),Smad3 and α-smooth muscle actin (α-SMA) were analyzed by immunohistochemistry and reverse transcriptase polymeric chain reaction.Results The area of alveolar septum and collagen in the lungs as well as the collagen production inereased in group B which were attenuated by EM.There was no statistical siganificance between group D and group E.The protein and mRNA expressions of TGF-β1 and α-SMA as well as Smad3 mRNA were increased in group B and were attenuated by EM.The expression of Smad3 in plasma in group B was attenuated while in nucleus enhanced.Smad3 expression decreased in nucleus but enhanced in plasma.The change in group C was the most obvious,while there was no statistieal significance beteen group D and group E.Conclusions EM can prevent the development of pulmonary fibrosis in rats,which might due to influce the signaling mediated by TGF-β1/Smad3 and then inhibit the lung fibroblasts proliferation and collagen production. Key words: Erythromycin; Pulmonary fibrosis; Signaling pathway; Transforming growth factor-β1 ; Smad3