| Objective:The present study was undertaken to investigate the anti-fibrotic effects oferythromycin with the regulation on TGF-β/Smad signaling on blemycin-induced lungfibrosis in rats.Methods:Sixty healthy male SD rats(clean grade)were randomly divided into fivegroups:control group(group A),bleomycin group(group B),bleomycin and EM pretreatmentgroup (group C),bleomycin and erythromycin syntreatment group(group D),bleomycin anderythromycin post-treatment group(group E).Bleomycin was intratracheally administratedat a dose of5mg/kg for once to make the model of pulmonary fibrosis in rats except thegroup A on day0.The rats of group A were given equivalent volume of normal saline in thesame way.Erythromycin was administrated by oral at a dose of100mg/kg from day-3,0,7to28to the rats respectively in group C、group D and groupE，while the equivalent volumeof normal saline was administrated to the rats in group A and B in the same way.Allexperimental animals were sacrificed on day14and28,6rats each time,a total of30.Thelung specimens were harvested for HE stain and Masson stain to observe pulmonaryalveolitis and lung fibrosis;The content of Hyp was measured by alkaline hydrolysis,Whilethe expressions of protein and mRNA of TGF-β1、Smad3、Smad7and α-SMA wereanalyzed by means of immunohistochemistry(SP)and RT-PCR respectively.Results:①There were neither Widened alveolar septum and Interstitial inflammationnor fibrotic area and Honeycomb-like change in rats of lung tissues of group A showed byHE staining and Masson staining.In group B,there were infiltration of inflammatory cells,collagon deposition,destruction of lung tissue structure,and fibrotic area on day14, Collagen deposition and damage of alveolar structure and fibrosis were moreseriously,while pulmonary alveolitis was apparently easer on day28.The degree ofpulmonary alveolitis and fibrosis treated with erythromycin was improved compared withthat of group B.②The content of Hyp in group B dramatically increased compared withthat of group A,and the concentration on day28was highest. Erythromycin could reducehydroxyproline content,and the change in group C was the most obvious,while there wasno statistical significance between group D and group E.③Immunohistochemistry andRT-PCR showed that TGF-β1,Smad3and α-SMA ecpression remarkably increased ingroup B which were attenuated by erythromycin.The change in group C was moreobvious,while there was no statistical significance between group D and group E.Smad7expression was inhibited in group B,while was not improved by erythromycin.Conclusion:①Erythromycin may prevent and postpone bleomycin-induced pulmonaryfibrosis by adjusting the content of extracellular matrix in fibrotic rats and lightening theextent of pulmonary alveolitis and fibrosis.②The possible mechanisms of erythromycin onlung fibrosis may be associated with inhibiting the activation of TGF-β1/Smad3signaling、then suppressing fibroblasts proliferation and collagon deposition. |
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