Effects Of Vitamin D3 On Bleomycin-induced Pulmonary Fibrosis In Mice

Objective:To investigate the effects of Vitamin D3 on bleomycin(BLM)-induced pulmonary fibrosis in mice.Methods:96 adult male C57BL/6J mice(8 weeks,24~26 g)were randomly divided into eight groups: Control group,vitamin D3(VitD3)group,BLM 1 d,7 d and 21 d groups,and VitD3+BLM 1 d,7 d and 21 d groups.In bleomycin group,mice were intratracheally injected with bleomycin(3 mg/kg).In VitD3+BLM group,mice were intraperitoneally injected with 1,25(OH)2D3(1 ?g/kg)daily,beginning at 30 min before BLM injection.VitD3 mice were injected with 1,25(OH)2D3(1 ?g/kg)daily.Control mice were injected with saline daily.Mice were euthanized at 1 d,7d,and 21 d after BLM,respectively.Some lungs were collected for real-time RT-PCR.Some lungs were excised for histopathologic examination and immunohistochemistry.Results As expected,BLM-induced damage of alveolar structure and pulmonary fibrosis in mice.Of interest,1,25(OH)2D3 attenuated BLM-induced damage of alveolar structure and pulmonary fibrosis in mice.Further study found that BLM up-regulated oxidant enzyme gene expression and down-regulated antioxidant enzyme gene expression.1,25(OH)2D3 inhibited BLM-induced up-regulation of oxidant enzyme gene and down-regulation of antioxidant enzyme gene.Moreover,strong 3-nitrotyrosine immunoreactivity was observed in the lungs 1d,7d and 21 d after BLM injection.Of interest,1,25(OH)2D3 significantly attenuated BLM-induced protein nitration in the lungs.Conclusion:Oxidative stress is involved in bleomycin-induced pulmonary fibrosis in mice.Vitamin D3 protects against BLM-induced pulmonary fibrosis in mice via counteracting BLM-induced oxidative stress.