Vitamin D supplementation decreases the expression of TGF-β1 in rats with asthma and thereby suppressing airway remodeling / 中国医师杂志

ABSTRACT

Objective To investigate the preventive and therapeutic effects of 1,25-(OH) 2D3 on airway remodeling in asthmatic rats,and to explore the effect of 1,25-(OH) 2D3 on the expression of transforming growth factor-β 1 (TGF-β 1) and the related mechanism between them.Methods Seventy male Sprague Dawley (SD) rats were randomly divided into seven groupsnormal control group (group A,n =10),asthmatic group (group B,n =10),dexamethasone group (group C,n =10),1,25-(OH)2D3 2 μg/(kg·d) group (group D,n=10),1,25-(OH)2D3 4 μg/(kg · d) group (group E,n =10),1,25-(OH)2D3 8 μg/(kg · d) group (group F,n =10),1,25(OH)2D3 16 μg/(kg · d) group (group G,n=10).Rats were sensitized and challenged with ovalbumin (OVA) to establish the asthmatic model in B,C,D,E,F,G group respectively.Rats in group B and group C were fed with normal saline 10 ml/(kg · d) and dexamethasone 2 mg/(kg · d) before atomization.While group D-G was 1,25-(OH)2D3 intervention group,rats were fed with vitamin D 2,4,8,16 μg/(kg · d) before atomization.The number of total and different cells of the bronchoalveolar lavage fluid (BALF) from the 7 groups was counted for analysis;The change of the thickness,the area of airway wall and the number of ASMC nucleus and pulmonary tissue changes were observed by microscope.The protein and mRNA expression of TGF-β1 in the lung tissue was measured by immunochemistry and real-time polymerase chain reaction (RT-PCR).Results (1) The airway remodeling and pulmonary inflammatory exudation in the B group were significantly heavier than those in the A,C and G groups (P ＜0.01);and the difference between groups of different doses of vitamin D [D group (minimum dose) and G group(the maximum dose)] was statistically significant (P ＜ 0.01).(2) The results of TGF-β1 mRNA and protein levels in rats of each group showed that the expression level of TGF-β1 mRNA and integrated option density (IOD) value in A group were significantly lower than those in other groups (P ＜0.01);the expression level of TGF-β1 mRNA and IOD value in B group was higher than the other groups (P ＜0.01);Compared with the B group,the expression level of TGF-β1 mRNA and IOD value in G group (large dose vitamin D group) was decreased,with statistically difference.Conclusions In the rat model of asthma,1,25-(OH) 2D3 may alleviate airway remodeling by regulating the expression of TGF-beta 1 and play its opposite biological effect in the prevention and treatment of asthma.