布地奈德对哮喘气道重塑小鼠p-VEGFR2表达的影响及其机制研究
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江苏省卫生厅“科教兴卫工程”-呼吸病学学科(实验室)开放课题资助


Effects of budesonide on the expression of phosphorylated VEGFR2 in asthmatic mice with airway remodeling
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    摘要:

    目的:磷酸化研究血管内皮生长因子受体2(VEGFR2)在哮喘气道重塑小鼠肺组织中的表达水平以及布地奈德对其干预作用-方法:24只BALB/c小鼠随机分为正常组-哮喘组以及布地奈德干预组,每组8只;以鸡卵清蛋白(OVA)致敏-激发建立慢性哮喘气道重塑模型-布地奈德干预组OVA激发前30 min给予布地奈德混悬液10 ml雾化吸入-OVA末次激发结束后24 h处死小鼠后肺组织石蜡切片HE染色观察气道炎症及形态学改变,免疫组化法观察肺组织VEGFR2磷酸化水平-蛋白印迹法(Western blot)测定VEGFR2-Erk蛋白磷酸化水平-结果:HE染色示与对照组相比,哮喘组出现黏膜下层和平滑肌增厚,管腔狭窄,大量炎症细胞浸润的表现,布地奈德组上述改变较哮喘组为轻;免疫组化结果显示哮喘组磷酸化VEGFR2阳性细胞数较对照组明显升高(P < 0.01),布地奈德组较哮喘组降低(P < 0.05);Western blot结果显示哮喘组小鼠VEGFR2-Erk磷酸化水平表达较对照组明显升高(P < 0.01);布地奈德干预后VEGFR2及Erk磷酸化水平较哮喘组小鼠均明显降低(P < 0.01)-结论:哮喘气道重塑小鼠肺组织 VEGFR2-Erk磷酸化水平可能上调,布地奈德对VEGFR2及其下游通路Erk磷酸化水平的抑制作用可能是其减轻哮喘炎症以及气道重塑的作用机制之一-

    Abstract:

    Objective:To investigate effects of budesonide on the expression of phosphorylated vascular endothelial growth factor receptor 2(VEGFR2) in asthmatic mice with airway remodeling. Methods:Twenty-four BALB/c mice were randomly divided into control group, asthma group and budesonide intervention group. The mice were sensitized and challenged with ovalbumin(OVA) to establish the chronic asthmatic model. Budesonide (10 ml) was atomized half an hour before sensitization in budesonide intervention group. After finished the last sensitization for 24h, the mice were sacrificed. Right lungs were isolated and stained with haematoxylin and eosin (HE). Immunohistochemistry was used to detect the expression of phosphorylated VEGFR2, and Western blot was applied to examine the expressions of phosphorylated VEGFR2 and Erk in the left lungs. Results:There were bronchial airway remodeling and mass inflammatory cells infiltration in asthmatic group; budesonide intervention ameliorated the symptoms mentioned above significantly. The protein expression levels of phosphorylated VEGFR2 and Erk in asthmatic group were higher than those of the control group(P < 0.01), and both of them decreased dramatically in the budesonide intevention group(P < 0.01). Conclusion:The expressions levels of phosphorylated VEGFR2 and Erk in asthmatic mice were much higher than control group, and budesonide could inhibit phosphorylation of them, thus relieve airway inflammation and delay the process of airway remodeling.

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李涛,黄茂,刘红,刘媛.布地奈德对哮喘气道重塑小鼠p-VEGFR2表达的影响及其机制研究[J].南京医科大学学报(自然科学版),2011,(3):308-313

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  • 收稿日期:2010-09-20
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