The Effects Of Metforminon Bleomycin-induced Pulmonary Fibrosis In Rats

Objective:To study the effects of metformin of AMPKactivation on bleomycin-induced pulmonary fibrosisin rats.Methods: 32 Male SD rats, weighted 180.0-200.0g, were randomly divided into control,model,metformin,and prednisone groups(8 rats in each group).Rats in model,metformin,prednisone groups were injected with a single dose of bleomycin(5mg/Kg)through tracheaand control group with the normal saline(1ml/Kg).After the injection,the rats of four groups were fed different drugs, the control and model groups(normalsaline 5ml/Kg/d), metformin group(metformin 250 mg/Kg/d),and prednisone group(prednisone 5mg/Kg/d),for fourteen days. On the fifteenth day after injection, all rats in treatmentwerekilled for taking samples. Serum and bronchoalveolarlavage fluid(BALF) were harvestdto determine the levels of transforming growth factor- β(TGF- β) and lung tissue sampleswere harvested to determinetheconcentration ofhydroxyproline(HYP) by enzyme-linked immunosorbent assay(ELISA),using HE and Masson staining pathology to observe the changes of the lung tissue biopsy sections.Results: compared with control group, in model group the score of lung alvelitis and pulmonary fibrosis in lung tissue, HYP content in lung tissue,TGF-β content in serum and BALFbecame higher(P<0.05); compared with model group, in metformin and prednisone groups the score of lung alvelitis and pulmonary fibrosis in lung tissue, HYP content in lung tissue,TGF- β content in serum and BALF becamelower(P<0.05); compared with prednisone group, in metformin group the score of pulmonary fibrosis in lung tissue, HYP content in lung tissue,TGF-β content in serum and BALF becamelower(P<0.05),but score of lung alvelitis in lung tissue became higher(P>0.05).Conclusion:1.metformin has an obvious inhibiting effect on bleomycin-induced pulmonary fibrosisin rats. 2. Metformin in the mechanisms of pulmonary fibrosis may be through activation of AMPK to reduce TGF-βcontent.