Effect and mechanism of TGF-β1/smad3 signal pathways on apoptosis during mice pulmonary fibrosis / 中华老年医学杂志

ABSTRACT

Objective To explore the effect and mechanism of TGF beta1/smad3 signaling pathways on apoptosis in mouse pulmonary fibrosis.Methods Fifty-four healthy male C57BL/6 mice were randomly divided into three groupsnormal control (n=18),pulmonary fibrosis model (n =18) and TGF-β1/smad3 inhibitor group (n=18).Six mice in each group were randomly killed on days 7,14 and 28.Hematoxyli~eosin and Masson staining were adopted to evaluate the severity of pulmonary inflammation and fibrosis.The content of hydroxyproline (Hyp) in the lung tissues was detected by alkaline hydrolysis technique.The apoptosis was observed by tunnel apoptosis assay kit.P-smad3 and caspase3 protein expressions were assessed via Western blot.Results Lung in model mice versus normal control showed alveolar inflammatory change in 7 days and significant pulmonary fibrosis in 28 days(P＜0.05).Meanwhile,apoptosis index,hydroxyproline content,caspase3,and phosphorylated Smad3 were obviously higher in model mice than in control group (P ＜ 0.05).Compared with model group,TGF-β1/smad3 inhibitor group showed that alveolitis and pulmonary fibrosis degree,hydroxyproline content,cell apoptosis index,the expressions of p-smad3 and caspase3 were decreased at same time point (P ＜ 0.05).Conclusions TGF beta1/smad3 signaling pathways may participate the abnormal apoptosis during the development of pulmonary fibrosis,and TGF-β1/smad3 inhibitor SB431542 could inhibit this process.