【摘要】 目的观察布地奈德对慢性支气管哮喘(简称哮喘)小鼠转化生长因子β1(transforming growth factor-β1,TGF-β1)/Smad信号通路的影响。方法30只小鼠按随机数字表法分成哮喘组、布地奈德组、正常对照组,每组10只。哮喘组小鼠于第0天和第14天以卵白蛋白(OVA)致敏,第24天开始雾化吸入1%OVA激发并持续28d,建立哮喘气道重塑模型;布地奈德组在吸入OVA前2h雾化吸入布地奈德30min;正常对照组以生理盐水代替OVA。于最后一次雾化结束后24h对肺组织行苏木精-伊红染色观察病理学改变;运用医学图像分析软件测定管腔内周长(Pi)、管壁面积(WAt)、支气管平滑肌面积(WAm)、支气管平滑肌细胞核数(N),将WAt、WAm、N用Pi标准化;用免疫组织化学方法检测肺组织TGF-β1蛋白表达;用逆转录-聚合酶链反应半定量检测肺组织TGF-β1、Smad2、Smad3、Smad7mRNA表达。结果哮喘组WAt/Pi、WAm/Pi、N/Pi与对照组比较差异有统计学意义(P值均<0.05),布地奈德组与哮喘组比较差异也具有统计学意义(P值均<0.05);哮喘组TGF-β1蛋白和TGF-β1、Smad2、Smad3mRNA的表达较对照组增加,差异有统计学意义(P<0.05),布地奈德组TGF-β1蛋白和TGF-β1、Smad2、Smad3mRNA的表达下降,与哮喘组比较差异均有统计学意义(P<0.05);布地奈德组可显著上调Smad7mRNA的表达,与哮喘组比较差异有统计学意义(P<0.05)。结论早期雾化吸入布地奈德通过抑制慢性哮喘小鼠肺组织TGF-β1、Smad2、Smad3的过度表达,上调Smad7的表达,从而阻断TGF-β1/Smad信号通路,明显减轻哮喘小鼠的气道重塑。更多还原

【Abstract】 Objective To observe the effects of aerosol budesonide on the airway remodeling and the expression of transforming growth factor-β1(TGF-β1),Smad 2,Smad 3,Smad 7 in an asthmatic mouse model.Methods Thirty BALB/c mice were divided into model group,budesonide group and normal group,ten in each group.Model group was sensitized on days 0 and 14 by ovalbumin(OVA)and challenged from days 24 to 51 by OVA repeatedly to establish a chronic model of asthma characterized by airway remodeling.Budesonide group was interfered with aerosol budesonide 30 min before challenge.Normal group was treated with saline instead of OVA.The airway wall thickness(WAt/Pi),bronchial smooth muscle thickness(WAm/Pi),bronchial smooth nucleus counts(N/Pi)were measured by image analysis system.The expression of TGF-β1,TGF-β1 mRNA,Smad 2 mRNA,Smad 3 mRNA,Smad 7 mRNA were detected by immunohistochemistry and RT-PCR.Results ①WAt/Pi,WAm/Pi,N/Pi in model group were all significantly higher than those in normal group(P<0.05),while decreased in budesonide group(P<0.05).②The expression of TGF-β1,TGF-β1 mRNA and Smad 2,Smad 3 mRNA in model group were higher than those in normal group(P<0.05),while decreased in budesonide group as compared with model group(P<0.05).③The expression of Smad 7 mRNA in budesonide group was significantly higher than that in model group.Conclusions Budesonide inhalation could decrease the expression of TGF-β1,TGF-β1 mRNA,Smad 2,Smad 3 mRNA,increase the expression of Smad 7 mRNA in a chronic asthmatic mouse model and inhibit airway remodeling.更多还原