Effect of atorvastatin on MMP-9 and TIMP-1 levels in bronchoalveolar lavage fluid and serum of rats with bleomycin-induced pulmonary fibrosis

Abstract

To investigate the effects of atorvastatin on matrix metalloproteinase-9 (MMP-9) and the tissue inhibitor-1 of matrix metalloproteinase (TIMP-1) levels in bronchoalveolar lavage fluid (BALF) and serum of rats with experimental pulmonary fibrosis. Pulmonary fibrosis was induced by intratracheal administration of bleomycin in 30 female rats, which were further divided into two groups: Group M (without treatment) and Group A (treated with atorvastatin 10 mg/kg); control group (n = 5, Group C) was intratracheally administrated with same volume of saline. Five animals were sacrificed at 2 weeks (M2 and A2), 4 weeks (M4 and A4) and 6 weeks (M6 and A6) after model establishment, respectively. Lung tissue samples were harvested and prepared for HE and Masson's trichrome staining. Concentrations of MMP-9 and TIMP-1 in BALF and serum were measured by ELISA. The severity of inflammation and pulmonary fibrosis was significantly reduced in Group A than that in Group M, especially at week 6. No significant difference was noted in the serum concentrations of MMP-9 and TIMP-1 among the Group M, A and Group C. The BALF concentrations of MMP-9 in Group M2 and M6 were significantly higher than those in Group C (P < 0.01 and 0.05), whereas those in the atorvastatin groups (A2, A4 and A6) were lower than those in M2, M4 and M6. Although the MMP-9 was still higher in Groups A2 and A4 than in the Group C, there was no significant difference in MMP-9 between Group A6 and Group C. TIMP-1 levels in BALF were significantly higher in M4 and M6 than Group C (P < 0.01 and 0.05), there were no significant differences between Group M2 and Group C. The TIMP-1 levels in BALF of atorvastatin groups were significantly lower than those of model groups and control group (P < 0.01 and 0.05), which resulted in a significantly increased ratio of MMP-9 to TIMP-1 in the atorvastatin groups. Atorvastatin inhibits the synthesis and release of MMP-9 and TIMP-1 in the lung tissue of rats with bleomycin-induced pulmonary fibrosis, and has no significant effect on circulating MMP-9 and TIMP-1, which may be associated with the attenuation of experimental pulmonary fibrosis in rats.