The Effect Of Prx-1 On Inhibiting Pulmonary Fibrosis In Mice With Silicosis

Objectives Peroxiredoxin-1(Prx-1)is newly found to decrease reactive oxygen species(ROS)effectly,but the role in silicotic fibrosis keeps unclear.This study is to observe wether Prx-1 has a prohibited effect on silicosis-induced pulmonary fibrosis,and explore wether this effect is mediated by inhibition of oxidative stress and mitogen-activated protein kinase(MAPKs)signaling activation.Methods Forty C57BL/6 mice with 8 weeks old were randomly divided into 4 group: control group,SiO2 group,SiO2+vehicle group,and SiO2+Prx-1 group perspectively.Control and SiO2 group received saline or silica by trachea instillation.SiO2+vehicle group and SiO2+Prx-1 group received control lentiviral vector or Prx-1 lentiviral vector with silica perspectively.All animals were observed for 12 weeks.At the end of 12 weeks,they were euthanized and subjected to systemic circulation perfusion.Left lung were fixed for H.E.staining,while right lungs were used to do protein assay.The expression of Prx-1 and ?-smooth muscle actin(?-SMA)were measured by immunihistochemical staining.Immunofluresence was employed to detect the 8-OHd G level(a indicator of ROS).The expression of p-ERK1/2,p-P38,p-JNK,collagen type ? and ? were measured by western blot.Results 1 As the results of H.E.staining showing,pulmonary structure was normal in control group.SiO2 signicanlty induced silicotic lesions.Compared with SiO2 group,control lentiviral vector had no influnence on the morphological changes stimulated by SiO2,while Prx-1 transfection inhibited those changes obviously.2 The levels of ?-SMA and Prx-1 were much higher in SiO2 group than the control.Compared with SiO2 group,control lentiviral vector had no effect on ?-SMA and Prx-1 expressions,while ?-SMA was lower and Prx-1 was higer in SiO2+ Prx-1 group(P<0.05).3 Sililarly to ?-SMA and Prx-1 expression,8-OHd G was induced by SiO2,which can not be prohibited by control lentiviral vector but do by Prx-1 transfection(P<0.05).4 The expression of p-ERK1/2,pP38,p-JNK,collagen ? and ? were all increased in SiO2 group and SiO2+vehicle group,of which there was no difference.Compared to SiO2 group,the increased expression of them were reserved by treatment with Prx-1(P<0.05).Conclusions Prx-1 has an inhibitive effect on SiO2-induced pulmonary fibrosis,mediating by decrease in ROS and inhibition of MAPKs pathway activation,which has a role in reducing myofibroblasts differentiation.