Therapeutic Effect Of Rosiglitazone On Hormone Resistance In Obese Asthmatic Mice And Its Relationship With IL - 17

Objective To explore the therapeutic effect of rosiglitazone on the glucocorticoid resistance of obese mice with asthma and its relationship with IL-17. Methods The chronic asthma mice models and obesity mice model were established by OVA sensitization and challenge and fed with high fat diet in 105 female C57/6J mice which were randomly divided into seven groups, Normal group(group A), Asthma group(group B), Obese asthma group(group C), Budesonide group(group D), Dexamethasone group(group E)and Rosiglitazone group(group F), Dexamethasone rosiglitazone combined group(group G). All mice were sacrificed 24 hours after the last challenge. Broncho alveolar lavage fluid(BALF) was collected for leukocytes count and analysis. Serum IL-17 was detected by ELLISA. The airway inflammation and remodeling indices, including inflammation score, total bronchial wall area(WAt), smooth muscle area(WAm),and bronchial basement membrane perimeter(Pbm), were measured in the airway pathological slices with HE staining, PAS staining and Masson staining. Results Asthma attack was developed after challenges in the groups B~G except group A. There were no mice died in group A and group B, there were 2 mice in group C, 1 mouse in group D, 5 mice in group E and 1 mouse in group F and G died before the operation day. The leukocyte numbers of BALF, the inflammation score of pathological slices, WAt/Pbm and WAm/Pbm and serum IL-17 in group C are much higher than group A and group B. The leukocyte numbers of BALF and the inflammation score of pathological slices were decreased after Budesonide and Dexamethasone treatment in group D and group E. Serum IL-17 was reduced in E group significantly when compared with group C(P<0.05), there were no statistical difference between group C and group D. The leukocyte numbers of BALF, the inflammation score of pathological slices, WAt/Pbm and WAm/Pbm and serum IL-17 in group F and group G were decreased than group C significantly, the group G has a significantly decreased than group F(P<0.05). Conclusion The obese asthmatic mice were insensitive to glucocorticoid therapy, nebulized budesonide can reduce the airway inflammation in obese asthma, but no benefit in systemic inflammation and airway remodeling. Oral dexamethasone can decrease serum IL-17 concentration and reduce the airway inflammation but no benefit on airway remodeling and mortal rate. Rosiglitazone can improve airway remodeling and airway inflammation and reduce the level of interleukin 17. After combined rosiglitazones, it can improve airway remodeling and reduce dexamethasone related mortal rate and have a good supplementary function for glucocorticoid.