表皮生长因子受体对哮喘小鼠气道重塑的影响及机制

Effect of epidermal growth factor receptor on airway remodeling in asthmatic mice and its mechanism

摘要:

目的：探讨哮喘小鼠气道重塑与表皮生长因子受体（EGFR）、肝素结合性表皮生长因子（HB-EGF）的关系以及EGFR酪氨酸激酶抑制剂（AG1478）对气道重塑的干预作用。方法：建立哮喘小鼠气道重塑模型，对肺组织切片行Masson和过碘酸雪夫（PAS）染色分别显示胶原沉积和气道黏膜杯状细胞增生情况。应用免疫组化和RT-PCR方法分别检测HB-EGF的蛋白和EGFR、HB-EGF mRNA表达的变化。结果：哮喘组出现气道重塑的特征性改变，HB-EGF、EGFR表达水平增高。AG1478干预组较哮喘组气道重塑有所改善，EGFR、HB-EGF表达降低（P<0.05）。结论：EGFR参与哮喘小鼠气道重塑，其酪氨酸激酶抑制剂AG1478可缓解气道重塑过程。AG1478可能通过下调EGFR及HB-EGF的表达以及抑制依赖于EGFR下游的细胞信号转导级联反应来缓解哮喘气道重塑过程。［中国当代儿科杂志，2010，12（2）：137-140］

Abstract:

OBJECTIVE: To explore the relationship of airway remodeling with epidermal growth factor receptor (EGFR) and heparin-binding epidermal growth factor-like growth factor (HB-EGF) levels in asthmatic mice and the effect of EGFR tyrosine kinase inhibitor (AG1478) on airway remodeling. METHODS: Twenty-four male BALB/c mice were randomly divided into three groups: normal control, asthma, AG1478-treated. Mice were sensitized and challenged with ovalbumin (OVA) and a mouse mode1 of asthma was prepared. Collagen deposition was determined in Masson-stained lung sections. Periodic acid Schiff (PAS) staining was used to observe the proliferation of goblet cells. Immunohistochemistry was used to determine the protein expression of HB-EGF. RT-PCR was used to determine the mRNA expression of HB-EGF and EGFR. RESULTS: The characteristic changes of airway remodeling occurred in the asthma group. The expression of HB-EGF and EGFR in the epithelial cells of bronchi in the asthma group was significantly higher than that in the normal control group. Compared with the asthma group, the AG1478-treated group had decreased inflammation reactions, decreased collagen deposition and proliferation of goblet cells and lower expression of EGFR and HB-EGF. CONCLUSIONS: EGFR tyrosine kinase inhibitor (AG1478) ameliorates the progression of airway remodeling in mice with asthma by inhibitions of EGFR and HB-EGF expression and EGFR signal pathway.［Chin J Contemp Pediatr, 2010, 12 (2):137-140］