【Animal modeling】-Effect of astragaloside Ⅱ on IL-21/STAT3 pathway and airway inflammation in juvenile asthmatic rats

  Objective To investigate the effect of astragaloside Ⅱ on interleukin-21 ( IL-21 ) / signal transducer and activator of transcription 3 ( STAT3 ) pathway and airway inflammation in juvenile asthmatic rats.

  Methods The juvenile rats were randomly divided into control group, model group, astragaloside Ⅱ low, medium and high dose groups and dexamethasone group, with 12 rats in each group. Except the control group, the other groups were stimulated with ovalbumin (OVA). The juvenile rat asthma model was prepared, the juvenile rats in each group were treated with corresponding drugs, the airway reactivity (Penh value) was detected, and the serum and bronchoalveolar lavage fluid (BALF) supernatant were detected by enzyme-linked immunosorbent assay (ELISA) method. The contents of interleukin-6 (IL-6), interleukin-21 (IL-21) and transforming growth factor-β1 (TGF-β1) in the fluid; hematoxylin-eosin (HE) staining was used to observe the lung tissue of young rats Pathological changes; Western blot was used to detect the protein expressions of IL-21, phosphorylated-STAT3 (p-STAT3) and STAT3 in the lung tissue of juvenile rats.

  Results Compared with the control group, the bronchial epithelial structure disorder, edema and shedding of epithelial cells, inflammatory cell infiltration and other pathological changes in the lung tissue of juvenile rats in the model group were observed. Number of eosinophils, neutrophils, lymphocytes and macrophages, IL-6, IL-21 and TGF-β1 contents in BALF supernatant and serum, lung tissue inflammation score, IL-21, p -STAT3 protein expression was significantly increased (P<0.05). Compared with the model group, the astragaloside II treatment groups and the dexamethasone group of juvenile rats had gradually complete lung tissue structure, and the Penh value, the total number of leukocytes in BALF, eosinophils, neutrophils, lymphocytes after Ach challenge with different concentrations were significantly higher than those in the model group. The numbers of cells and macrophages, IL-6, IL-21 and TGF-β1 contents in BALF supernatant and serum, lung tissue inflammation score, and IL-21 and p-STAT3 protein expressions in lung tissue were significantly decreased (P<0 .05). And with the increase of astragaloside Ⅱ dose, the Penh value, the total number of leukocytes, eosinophils, neutrophils, lymphocytes and macrophages, BALF supernatant and serum in BALF after challenge with different concentrations of Ach in juvenile rats were significantly increased. The contents of IL-6, IL-21 and TGF-β1, lung tissue inflammation score, and IL-21 and p-STAT3 protein expressions in lung tissue were decreased in turn (P<0.05).

  Conclusion Astragaloside Ⅱ may reduce the airway inflammation in juvenile asthmatic rats by inhibiting the IL-21/STAT3 pathway, repair the structure of lung tissue, and improve asthma symptoms.