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 totalantioxidant 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.
ObjectiveTo compare two different ways to establish mouse model with acute lung injury (ALI) via intratracheal instillation or intraperitoneal injection of lipopolysaccharide (LPS). MethodsBALB/c mice received intraperitoneal/intratracheal administration of LPS or sham operation. Wet/dry lung weight ratio, protein concentration in bronchoalveolar lavage fluid (BALF), and lung tissue histology were examined at 0, 1, 2, 6, 12, 18, 24, 48 h after LPS administration. Tumor necrosis factor-α (TNF-α) in BALF and serum was assayed with ELISA method. ResultsLPS treatment significantly increased wet/dry lung weight ratio, BALF protein concentration and TNF-α concentration in serum and BALF. Lung tissue was damaged after LPS challenge. The mice received LPS intraperitoneal injection got a more significant lung edema than those received LPS intratracheal instillation. Inversely, LPS intratracheal instillation induced more severed microstructure destruction. ConclusionsALI animal model by LPS intratracheal instillation or intraperitoneal injection induces inflammation and tissue damage in lung. However, the degree of tissue damage or self-healing induced by two methods is different. Therefore the decision of which way to establish ALI model will depend on the study purpose.