c-kit磷酸化与哮喘气道重塑的关系及布地奈德对其的影响

Effect of budesonide on airway remodeling and c-kit phosphorylation in a mouse model of asthma airway remodeling

目的:研究干细胞因子(stemcellfactor,SCF)/c-kit通路在气道重塑中的作用及糖皮质激素影响气道重塑的可能机制。方法:将30只BALB/c小鼠随机分为正常对照组、哮喘气道重塑组、布地奈德干预组,每组10只;鸡卵清蛋白致敏和激发建立哮喘小鼠气道重塑模型;HE染色观察各组气道炎症发生及气道结构改变情况;免疫沉淀/蛋白质印记(IP/Wb)法测定各组小鼠肺组织中c-kit受体磷酸化程度的变化。结果:HE染色提示哮喘组与对照组相比出现黏膜下层和平滑肌增厚,气道管腔狭窄,大量炎细胞浸润的表现,布地奈德组上述改变较哮喘组为轻;IP/Wb检测发现磷酸化的c-kit受体在哮喘组表达较对照组为高(P<0.01),而布地奈德组表达量低于哮喘组(P<0.01)。结论:c-kit受体磷酸化可能在哮喘气道重塑过程中表达上调;布地奈德抑制c-kit受体磷酸化可能是其减轻气道炎症和气道重塑的机制之一。

Objective：To investigate the role of SCF （stem cell factor）/c-kit pathway in airway remodeling and the influence of glucocorticoids on airway remodeling and its mechanisms. Methods：Thirty BALB/c mice are evenly divided into three groups at random. They are normal group, the group of asthma airway remodeling and the group of budesonide intervention. All the mice were sensitized and challenged with ovalbumin to establish the asthmatic model. The airway inflammation and the alteration of airway structure were observed by the means of hematoxylin and eosin staining. Expression of phosphorylated c-kit was examined by im- munoprecipitation/Western blot analysis. Results：It is indicated that the incrassation of submucosa and smooth muscle,airway stenosis and mass inflammatory cells infiltration were identified more significantly in the asthmatic group than that in the control group. As far as the therapeutic group was concerned,the above-mentioned symptoms were lighter than that of the asthmatic group. The protein expression level of phosphorylated c-kit in asthmatic group was higher than that of the normal group （P 〈 0.01 ）,while it is decreased in therapeutic group （P 〈 0.01）. Conclusion：The expression of phosphorylated c-kit in asthmatic group might be higher than that of the normal group, and budesonide could inhibit the phosphorylation of c-kit receptor, thus relieve airway inflammation and airway Temodeling.