Valproate which is a histone deacetylase inhibitor effected the inflammation of pulmonary fibrosis in mice

Abstract

Objective To explore the effects of valproate,a histone deacetylase inhibitor (HDACI)of,on the expression of TNF-α in mice with bleomycin-induced pulmonary fibrosis.Methods SD mice were randomly divided into three groups,ie.a control group (CG),a bleomycin-induced pulmonary fibrosis model group (MG) and a sodium valproate-treated group (VG).The mice in CG received a single intratracheal dose of 2 ml/kg of sterile physiological saline at day 0.MG and VG were induced by a single intratraeheal dose injection of bleomycin-A5 (5 mg/kg).The mice in MG were intraperitoneally injected with sterile physiological saline (0.5 ml/d) and the rats in VG were intraperitoneally treated with sodium valproate.After treament 12 rats in each group were randomly killed on day 7,respectively.Lung tissues were taken and processed for determination hydroxyl proline contents,the expression of TNF-α and Szapiel scores.Bronehoalveolar lavage fluid (BALF) was collected for measurements of total and differential cell counts and lactic dehydrogenase (LDH) levels.Results It was found that the number of macrophage,and the LDH contentsfrom the mice treated with bleomycin alone sacrificed on the day 7 were increased compared with the mice in CG ( P ＜0.01 ).the hydroxyl proline contents,the expression of TNF-α were greatly increased ( P ＜0.05).However,Szapiel scores,LDH contents,hydroxyl proline contents,the expression of TNF-α were greatly reduced in the mice treated with bleomycin followed by valproate.Conclusions This study indicates that administration of valproate to the mice suffered from pulmonary fibrosis induced by bleomycin attenuates the fibrosis greatly reducing the expression of TNF-α,via inhibiting early inflammation and inhibiting pulmonary fibrosis. Key words: Histone deacetylase inhibitor; Pulmonary interstitial fibrosis; Tumor neorosis factor-α