Role And Relational Mechanism Of AG490 In Airway Remodeling In The Mouse With Bronchial Asthma

Objective: To investigate the effects of JAK/STAT6 pathway in airway remodeling in the mice with bronchial asthma and influence of AG490 on airway remodeling and its mechanism.Methods: Thirty-two female BALB/c mice were divided into four groups randomly. They were the control group, the asthma group, the group of AG490 intervention and the group of budesonide intervention. The mice were sensitized and challenged with ovalbumin to establish the chronical asthma model. The airway inflammation and the collagen deposition in the lungs were observed by the means of HE and MASSON staining. The expression of p-STAT6 was examined by Western blot and immunohistochemistry analysis, while the content of cyclinD1 were dected by Western blot and RT-PCR.Results: There were bronchial smooth muscle hypertrophy, submucosa incrassation, airway stenosis, collagen fiber increase and mass inflammatiory cells infiltration in asthma group. In AG490 and budesonide intervention groups, the above mentioned symptoms were clearly ameliorated. The protein expression level of p-STAT6 and cyclin D1 in asthmatic group were higher than the control group(p<0.01), but they were decreased in AG490 and budesonide intervention group(sp<0.01). The level of cyclinD1 mRNA in asthmatic group was higher than control group(p<0.01), lower than the AG490 and budesonide intervention groups(p<0.01). Compared with the control group, the expression of p-STAT6 in asthmatic group were much more(p<0.01), the level of p-STAT6 in AG490 and budesonide intervention group (p<0.05)were between them.Conclusions:: JAK/STAT6 signal pathway involves in airway inflammation and remodeling of asthma. AG490 may ameliorate the progression of airway inflammation and remodeling through regulation of JAK/STAT6 signal pathway.