Valproate modulated expression of transforming growth factor-β1 in mice with bleomycin-induced pulmonary fibrosis

Objective To explore the effects of valproate,a histone deacetylase inhibitor on the expression of transforming growth factor-β1 (TGF-β1) in mice with bleomycin-induced pulmonary fibrosis,Methods Fifty-four SD rats were randomly divided into three groups (18 rats in each group):control group (CG),bleomycin-induced pulmonary fibrosis model group (MG) and sodium valproate-treated group (VG),each group also divided into three batches:day 7,14 and 28.The rats in CG received a single intratracheal dose of 0.3 ml sterile physiological saline at day 0.The rats in MG and VG were induced by a single intratraeheal dose injection of bleomycin-A5 (5 mg/kg)with sterile physiological saline soultion.The rats in MG were intraperitoneally injected with sterile physiological saline (0.5 ml/d)and the rats in VG were intraperitoneally treated with sodium valproate (200 mg· kg-1 · d-1 ).After treament 18 rats in each group were randomly killed on day 7,14 and 28.Their lungs were harvested for measurement of the pathological change in lung tissues.The sections of lungs were stained with HE for histopathology study to evaluate the severity of alveolitis and pulmonary fibrosis.Masson's trichrome was used to determine the content of hydroxyproline in lung samples.Collagen was assessed by the content of hydroxyproline in lung tissues.The expression of TGF-β1 in lung tissues was observed by histoimmunochemical staining and these indexes were analyzed through SPSS 13.0 statistical software.Results It was founded that the hydroxyproline contents and Szapiel scores,the expression of TGF-β1 from the rats with bleomycininduced pulmonary fibrosis were greatly increased ( P ＜0.01 ).However,the hydroxyproline contents and Szapiel scores,the expression of TGF-β1 were greatly reduced in the mice treated by valproate and sacrificed on the day 14,28 compared with those induced with bleomycin alone.Conclusions This study indicates that administration of valproate to the mice suffered from pulmonary fibrosis induced by bleomycin attenuates the fibrosis via inhibiting the expression of TGF-β1 and reducing the Masson's trichrome in the lung. Key words: Histone deacetylase inhibitor;  Pulmonary interstitial fibrosis;  Transforming growth hctor-β1