Abstract: Objective To explore the effect of 1, 25-dihydroxyvitamin D3［1, 25-(OH)2D3］on reactive oxygen species
(ROS) through transforming growth factor- β1(TGF- β1)/(Smad2/3) and molecular mechanism of regulating airway
remodeling. Methods Twenty-four healthy female Balb/c mice were randomized into control group (group A), asthma group
(group B), and asthma treated with 1, 25-(OH)2D3 group (group C). The group B and group C were sensitized with ovalbumin via intraperitoneal injection at the day 0, 7, and 14, and ovalbumin was also given by aerosol inhalation, once a day from the day 21 to 27, and once every other day from day 28 to 77 to build the airway remodeling model of bronchial asthma of mice.
Group C was given 100 ng of 1, 25-(OH)2D3 via intraperitoneal injection half an hour before each aerosol challenge, and the experimental process lasted at least 77 days. The lung tissues of mice were collected for HE staining, AB-PAS staining, and Masson staining to analyze the airway pathological changes, high secretion of airway mucus, and airway remodeling status. The computer image analysis system was used to evaluate the airway remodeling. Airway ROS expression was tested by immunofluorescence. The expression levels of TGF- β1 and Smad2/3 were tested with Western blot assay. Results Compared with group A, the airways was significantly damaged in group B with large amount of inflammatory cell infiltration, increased mucus secretion and increased subepithelial collagen deposition. Compared with group B, the pathological and morphological damages were significantly relieved in group C, but still more severe than those of group A. The expression levels of ROS, TGF-β1 and Smad2/3 proteins were significantly higher in group B than those in group A. Compared with group B, the expressions of ROS, TGF- β1 and Smad2/3 proteins were reduced in group C, but still higher than those in group A (P＜0.01). Conclusion 1, 25- (OH)2D3 may reduce the ROS level by inhibiting the expressions of TGF- β1/(Smad2/3), and thereby regulating the airway remodeling in mice.

Key words: calcitriol, asthma, airway remodeling, reactive oxygen species(ROS), transforming growth factor-β1(TGF-
β1), 1, 25-dihydroxyvitamin D3