FIZZ1及NOTCH1在哮喘中的作用

Roles of FIZZ1 and NOTCH1 in asthma

摘要:

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。

Abstract:

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.