Effects of 1, 25-(OH)2D3 on idiopathic pulmonary fibrosis of rats and its mechanism

DONG Hongliang; LIU Naiguo; MIAO Shuang; ZHENG Jing; NI Na; WANG Nan

doi:10.3969/j.issn.1002-266X.2016.28.006

Abstract：Objective To observe the effects of 1, 25-(OH)2 D3 on idiopathic pulmonary fibrosis (IPF) of rats, and to in-vestigate its mechanism.Methods Ninety male SD rats were randomly divided into the model group, treatment group and con-trol group (n=30 each).Bleomycin (5 mg/kg) was injected to the trachea of rats to establish the model of pulmonary fibrosis in the model group and treatment group, while the control group was injected with normal saline (200μL in each).From the fol-lowing day, rats in the treatment group and model group received 1, 25-(OH)2D3(2μg/kg) and solvant (200μL for each), re-spectively and once every other day.The control group was treated with normal saline (200 μL for each).Ten mice in each group were killed randomly on day 14, 21 and 28.The hydroxyproline content of lung tissues was measured by basic-hydrolysis method.Lung fibroblasts were separated from lung tissues and labeled by Fluo-3AM, then we used Laser scanning confocal mi-croscope to detect the concentration of Ca2+.The mRNA levels of PI3K, AKT and mTOR in the lung fibroblasts were tested by real-time PCR.Results The hydroxyproline content of lung tissues, the Ca2+concentration and expression of PI3K, AKT and mTOR in lung fibroblasts were increased in the model group as compared with that of the control group on day 14, 21 and 28. The above indicators of treatment group were reduced significantly as compared with those of the model group (P<0.05 or P<0.01).Ca2+concentration was positively correlated with mRNA expression levels of three genes in the model group and treatment group (r=0.784, 0.647, 0.805, all P<0.01).Conclusion 1, 25-(OH)2D3 inhibits the occurrence and development of IPF in rats, and its mechanism may be the reduction of Ca2+concentration and inhibition of PI3K-AKT-mTOR pathway.