Objective To evaluate the effects of N-acetylcysteine ( NAC) on bleomycin-induced lung fibrosis in mice and to investigate the therapeutic mechanisms of NAC on lung fibrosis.
Methods Forty-five KM female mice were randomly divided into 3 groups. The mice in the control group were administered with saline aerosol intratracheally. The mice in the fibrosis group were administered with bleomycin ( 3 mg/kg) dissolved in normal saline aerosol intratracheally. The mice in the NAC group were gastric perfused with NAC at a dose of 400 mg · kg- 1 · d - 1 after administering bleomycin aerosol intratracheally. All animals were sacrificed 28 days after the treatments. The left lung was fixed in 10% neutral formalin, then stained with hematoxylin eosin and Masson’s trichrome respectively for the pathological examination. The right lung was sampled and the content of hydroxyproline ( HYP) was assayed by alkaline hydrolysis method. The serum was collected and the concentrations of malondialdehyde ( MDA) and total
antioxidant capacity ( T-AOC) were measured by colorimetric method. The RNA and total tissue protein were extracted for the examination of NOX1 /2/4 by RT-PCR and Western blot respectively.
Results NAC prevented lung fibrosis induced by bleomycin with significantly reducing lung collagen accumulation and the level of HYP in the NAC group ( P lt;0. 05) . The serum concentration of MDA were reduced and serum TAOC raised by treating NAC after intratracheal administration of bleomycin ( P lt;0. 05) . NOX1 /2/4 gene and protein expression were increased in the fibrosis group compared with the control group. NAC had no effect on the gene expression of NOX1/2 /4( P gt;0. 05) , but inhibitted the NOX4 protein expression in lung tissue significantly ( P lt; 0. 05) .
Conclusion NAC inhibits the expression of NOX4 and prevents bleomycin-induced lung fibrosis in mice.
Citation： HU Yujie,LI Li,LI Weifeng,HUANG Wenjie.. N-acetylcysteine Inhibits the Expression of NOX4 and Prevents Bleomycin-Induced Lung Fibrosis in Mice. Chinese Journal of Respiratory and Critical Care Medicine, 2013, 12(2): 153-157. doi: DOI: 10 . 7507 /1671 -6205 . 20130036 Copy