白三烯受体拮抗剂通过Wnt/β-catenin信号通路影响哮喘小鼠气道重塑机制的研究

Effects of a Leukotriene Receptor Antagonist on Airway Remodeling in Asthmatic Mice via the Wnt/β-catenin Signaling Pathway

目的探讨白三烯受体拮抗剂影响Wnt7b、β-catenin及c-Myc表达,干预哮喘小鼠气道重塑机制的研究。方法采用卵蛋白(OVA)致敏和激发建立小鼠哮喘模型。将小鼠分为对照组、哮喘组以及孟鲁司特钠组。HE染色观察各组小鼠气道炎症情况;ELISA法检测血清OVA-s Ig E水平;实时PCR和Western blotting分别定量分析肺组织中Wnt7b、β-catenin及c-Myc m RNA和蛋白表达水平;运用图像采集系统测定支气管管腔周长(PBM)、支气管管壁面积(WAt)、支气管管壁平滑肌面积(WAm)和平滑肌细胞计数(N),上述指标用PBM标准化。结果哮喘组小鼠血清OVA-s Ig E表达水平明显升高(P<0.05)。Western blotting以及实时PCR结果显示哮喘组Wnt7b、β-catenin及c-Myc蛋白和m RNA较对照组和孟鲁司特钠组表达均显著升高(P<0.05)。气道重塑指标WAt/PBM、WAm/PBM孟鲁司特钠组均低于哮喘组(P<0.05)。结论 Wnt/β-catenin信号通路可能是哮喘发病机制中的重要因素,白三烯受体拮抗剂(孟鲁司特钠)可能通过影响Wnt7b、β-catenin及c-Myc的表达干预哮喘气道重塑。

Objective To investigate the expression of Wnt7 b,β-catenin,and c-Myc in asthmatic mice and the intervention of the leukotriene receptor antagonist montelukast on airway remodeling. Methods The asthma model was established by ovalbumin（OVA） induction. HE staining was used to observe the pathological changes in lung tissue. Serum OVA-s Ig E levels were determined by ELISA. The level of Wnt7 b,β-catenin,and c-Myc protein and m RNA in the lung tissue of mice was analyzed by Western blotting and real-time PCR. The basement membrane perimeter（PBM）,wall area of bronchial tube（WAt）,wall area of bronchial smooth muscle（WAm）,and the number of smooth muscle cells were measured using medical image analysis software and standardized based on the PBM. Results The amount of OVA-slg E in the asthma group was significantly higher than in the control and montelukast groups（P 0.05）. Western blotting and real-time PCR showed that the expression of Wnt7 b,β-catenin,and c-Myc in the asthma group was higher than the expression in the control and montelukast groups（P 0.05）. Image analysis showed that the WAt/PBM and WAm/PBM ratios in the montelukast group were significantly lower than those in the asthma group（P 0.05）. Conclusion The Wnt/β-catenin signaling pathway may be an important factor in the pathogenesis of asthma;montelukast may attenuate airway remodeling in asthmatic patients by decreasing the expression of Wnt7 b,β-catenin,and c-Myc.