[Alphacalcidol combined with dexamethasone for reducing pulmonary fibrosis in mice and its mechanism].

Abstract

Objective To study the effect of alphacalcidol and dexamethasone on pulmonary fibrosis and its mechanism. Methods Forty C57BL/6 mice were randomly divided into five groups: normal control group, pulmonary fibrosis group, alphacalcidol group, dexamethasone group, dexamethasone combined with alphacalcidol group. The normal control group was given 0.5 μL/g normal saline by one-time intratracheal injection as well as 0.2 mL normal saline by daily intragastric infusion. The other groups received 0.5 μL/g bleomycin solution by one-time intratracheal injection; besides, the pulmonary fibrosis group were subjected to 0.2 mL normal saline gavage; the dexamethasone group were treated with dexamethasone [0.5 mg/ (kg.d)] orally; the alphacalcidol group received intragastric infusion of alphacalcidol [0.5 μg/ (kg.d)]; and the dexamethasone plus alphacalcidol group was given dexamethasone [0.5 mg/ (kg.d)] mixed with alphacalcidol [0.5 μg/ (kg.d)] orally. Then they were killed after 21 days. The pathological changes of lung tissues was observed using HE and Masson staining. The serum was collected to detect hydroxyproline (Hyp) values. Bronchoalveolar lavage fluid (BALF) was collected for cell counting. ELISA was performed to examine interleukin 1 beta (IL-1β), IL-6, tumor necrosis factor alpha (TNF-α) and transforming growth factor beta 1 (TGF-β1) in supernatants. Results In the alphacalcidol combined with dexamethasone group, IL-1β, IL-6, TNF-α and TGF-β1, cell count, Sazpiel score, Hyp values were lower than those in the other groups except for the control group, and the alveolar inflammation and fibrin deposition were also lower than those in the other groups except for the control group. Conclusion The curative effect of alphacalcidol combined with dexamethasone on pulmonary fibrosis is better than either dexamethasone or alphacalcidol alone, and the mechanism may be related to the inhibition of TGF-β1 and inflammatory factors.