Imatinib mesylate inhibits bleomycin-induced pulmonary fibrosis in mice: The mechanism / 第二军医大学学报

ABSTRACT

Objective: To observe the effect of imatinib mesylate on pulmonary fibrosis (PF) induced by bleomycin in mice and to explore the related mechanism. Methods: Totally 120 C57BL/6 mice were evenly randomized into control group, model group, dexamethasone group and imatinib group. The pulmonary fibrosis model was established using a single intratracheal infusion of bleomycin; the corresponding drugs were given to mice in each group. Ten mice was sacrificed in each group on day 7, 14, and 21 after operation, respectively. The expression of matrix metalloproteinase 1 (MMP-1), tissue inhibitor of metalloproteinase 1 (TIMP-1), and transforming growth factor β1(TGF-β1) in the lung tissues was semi-quantitatively analyzed by immunohistochemistry method. Results: Immunohistochemistry results showed that the expression of TIMP-1, MMP-1, and TGF-β1 in lung tissues of the dexamethasone group and imatinib group was significantly lower than that in the model group(P<0.01). There was a positive correlation between TGF-β1 and TIMP-1 expression(r=0.243, P=0.004). A negative correlation was found between MMP-1 and TIMP-1 in all the other 3 groups other than in the normal control group(r= -0.291, P<0.0001). Conclusion: Imatinib may downregulate TGF-β1 expression, inhibit TIMP-1 expression, and upregulate MMP-1 expression, maintaining the balance of TIMP-1/MMP-1, subsequently inhibit the development of pulmonary fibrosis, showing a similar effect of dexamethasone.