FIZZ1及NOTCH1在哮喘中的作用

Roles of FIZZ1 and NOTCH1 in asthma

目的探讨气道重塑中低氧诱导的有丝分裂因子(FIZZ1)和NOTCH1的表达及罗格列酮的干预作用。方法健康6～8周龄雄性Sprague-Dawley大鼠45只,分为哮喘组、对照组及罗格列酮干预组。制备肺组织石蜡切片进行病理学检查,免疫组化测定各组气道重塑特异性指标a-肌动蛋白(a-SMA)在肺组织中的表达,用RT-PCR方法测定各组肺组织中FIZZ1-mRNA及NOTCH1-mRNA的表达。结果哮喘组出现气道重塑的特征性改变,罗格列酮干预组气道病理学改变较哮喘组减轻。哮喘组a-SMA、FIZZ1-mRNA及NOTCH1-mRNA表达较对照组增高,罗格列酮干预后表达均显著降低,但仍高于对照组。a-SMA蛋白的表达与FIZZ1-mRNA及NOTCH1-mRNA的表达均呈正相关(r分别为0.826和0.9,P<0.01),FIZZ1-mRNA及NOTCH1-mRNA的表达成正相关(r=0.76,P<0.01)。结论 FIZZ1及NOTCH1可促使a-SMA表达增强,是引起哮喘早期气道重塑的重要炎症因子。罗格列酮可缓解气道重塑的过程。

Objective To investigate the roles of FIZZ1 and NOTCH1 in the pathogenesis of asthma and the effect of rosiglitazone on airway remodeling.Methods Forty-five healthy 6 to 8-week-old Sprague-Dawley rats were randomly divided into a control group and asthma groups with and without rosiglitazone treatment.The paraffin slices of lung tissues were made to assess the histological changes.a-SMA protein,a specific marker of airway remodeling,in lung tissues was measured by immunohistochemistry.FIZZl-mRNA and NOTCH1-mRNA expression in lung tissues was measured by RT-PCR.Results The characteristic changes of airway remodeling were observed in the untreated asthma group.The histological changes in the airway were less severe in the rosiglitazone treated asthma group.Positive a-SMA staining,FIZZl-mRNA and NOTCH1-mRNA were highly expressed in peribronchial lung sections isolated from the untreated asthma group.Rosiglitazone treatment decreased significantly the expression of a-SMA protein,FIZZl-mRNA and NOTCH1-mRNA compared with the untreated asthma group,but the expression of a-SMA protein,FIZZl-mRNA and NOTCH1-mRNA in the rosiglitazone treated asthma group remained higher than the control group.a-SMA expression was positively correlated with FIZZl-mRNA（r=0.826,P〈0.01） and NOTCH1-mRNA expression（r=0.9,P〈0.01）.FIZZl-mRNA expression was positively correlated with NOTCH1-mRNA expression（r=0.76,P〈0.01）.Conclusions FIZZl and NOTCH1 may induce an increase in a-SMA expression.FIZZl and NOTCH1 play a critical role in the process of airway remodeling.Rosiglitazone treatment may inhibit airway remodeling in asthmatic rats.