Inhibitory effect of atorvastatin on bleomycin-induced pulmonary fibrosis in rats and its mechanism

Objective To observe the inhibitory effect of atorvastatin on bleomycin-induced pulmonary fibrosis in SD rats and study their possible mechanism. Methods 30 male SD mice under SPF condition with average body weight of 250g were randomly allocated to three groups (n=10, each) of saline control group (control group), bleomycin-induced pulmonary fibrosis group (pulmonary fibrosis group) and atorvastatin treatment group (treatment group). Bleomycin (5mg/kg) (versus 0.2 ml saline in control group) were endotracheally instilled in pulmonary fibrosis group and the treatment group in order to establish the model of pulmonary fibrosis. Subsequently, the rats in the treatment group received daily atorvastatin (10 mg/kg) orally. 5 rats in each group were sacrificed on 7th and 28th day after intratracheal instillation. Their lung tissues were taken and tested. The histological changes in the lungs were evaluated by hematoxylin-eosin and masson stain. The tumor necrosis factor (TNF-α) level and hydroxyproline content in lung tissues were measured by enzyme-linked immunosorbent assay (ELISA). The expressions of Kruppel-like factor 2 (KLF2) protein and mRNA in lung tissues were measured by Western blotting and Real-Time PCR. Results The lung tissue in model group had significant bleeding and oozing inflammatory response on the 7th day and pulmonary fibrosis on the 28th day. Bleeding and oozing inflammatory response and pulmonary fibrosis were subdued in treatment group on the same days as compared to the model group. Hydroxyproline and TNF-α contents in lung tissue were significantly higher in model group than in control group (both P<0.05). KLF2 protein and KLF2-mRNA expressions in lung tissues were significantly lower in model group than in control group (both P<0.05). The above changes were partially reversed in treatment group. Compared to model group, treatment group showed that hydroxyproline and TNF-α contents in lung tissues were significantly reduced (both P<0.05) and KLF2 protein and KLF2-mRNA expressions in lung tissues were significantly increased (both P<0.05). Conclusions Atorvastatin can reduce the secretion of TNF-α and alleviate bleomycin-induced pulmonary fibrosis. The mechanism inhibiting fibrosis might be associated with up-regulation of KLF2-mRNA expression. Key words: Pulmonary fibrosis; Hydroxymethylglutaryl-CoA reductase inhibitors; Kruppel-like transcription factors