Effect of Sunitinib on Expressions of p-PDGFR-β and MMP-9 in Asthmatic Mice with Airway Remodeling

2009 
Objective: To investigate the effects of sunitinib on asthmatic airway remodeling and its possible mechanism.Meth-ods: BALB / c mice were randomly divided into three groups: normal group,asthmatic airway remodeling group and sunitinib interven-tion group.All the mice were sensitized and challenged with ovalbumin(OVA) to establish the asthmatic model.Bronchoalveolar lavage fluid(BALF) cell count and differential were carried out.The right lungs were isolated and stained with haematoxylin and eosin(HE) and Masson's trichrome.Expression of phosphorylated-PDGFR-β(p-PDGFR-β) was examined by immuno precipitation(IP),while MMP-9 expression was examined by Western blot analysis.Results: HE and Masson's trichrome staining showed that there were bronchial smooth muscle hypertrophy,submucosa incrassation,airway stenosis,collagen fiber increase and mass inflammatory cells infiltration in asthmatic group.In sunitinib intervention group,the above mentioned symptoms were much more ameliorated.The amounts of total leu-cocytes and eosinophils in BALF were significantly increased in asthmatic group(P0.05),compared with normal group.While the amounts of total leucocytes and eosinophils in BALF in therapeutic group was lower than that of asthmatic group(P0.05).The protein expression level of p-PDGFR-β and MMP-9 in asthmatic group was higher than that of the normal group(P0.01),but it was decreased in therapeutic group(P0.01).Conclusion: Sunitinib could inhibit the expression of p-PDGFR-β and MMP-9,thereby relieve airway in-flammation and delay the process of airway remodeling.
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