表皮生长因子受体对哮喘小鼠气道重塑的影响及机制

李晓辉; 栾斌

PDF(1453 KB)

中国当代儿科杂志 ›› 2010, Vol. 12 ›› Issue (2) : 137-140.

论著·实验研究

表皮生长因子受体对哮喘小鼠气道重塑的影响及机制

李晓辉，栾斌

作者信息 +

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

LI Xiao-Hui, LUAN Bin

Author information +

文章历史 +

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］

导出引用

李晓辉, 栾斌. 表皮生长因子受体对哮喘小鼠气道重塑的影响及机制[J]. 中国当代儿科杂志. 2010, 12(2): 137-140

LI Xiao-Hui, LUAN Bin. Effect of epidermal growth factor receptor on airway remodeling in asthmatic mice and its mechanism[J]. Chinese Journal of Contemporary Pediatrics. 2010, 12(2): 137-140

中图分类号： R562.2+5

参考文献

［1］ Sumi Y, Hamid Q. Airway remodeling in asthma［J］. Allergol Int, 2007, 56（4）:341-348.
［2］Tamaoka M, Hassan M, McGovern T, RamosBarbon D, Jo T, Yoshizawa Y et al. The epidermal growth factor receptor mediates allergic airway remodeling in the rat ［J］.Eur Respir J, 2008, 32（5）:1213-1223.
［3］Du Q, Chen Z, Zhou LF, Zhang Q, Huang M, Yin KS. Inhibitory effects of astragaloside Ⅳ on ovalbumin-induced chronic experimental asthma［J］. Can J Physiol Pharmacol, 2008, 86(7):449-457.
［4］Puddicombe SM, Polosa R, Richter A, Krishna MT, Howarth PH, Holgate ST, Davies DE. Involvement of the epidermal growth factor receptor in epithelial repair in asthma［J］.FASEB J, 2000(7), 14:1362-1374.
［5］Hamilton LM, Puddicombe SM, Dearman RJ, Kimber I, Sandstro¨m T, Wallin A et al. Altered protein tyrosine phosphorylation in asthmatic bronchial epithelium［J］.Eur Respir J, 2005, 25(6):978-985.
［6］Fedorov IA, Wilson SJ, Davies DE, Holgate ST. Epithelial stress and structural remodelling in childhood asthma［J］.Thorax, 2005, 60（10）:389-394.
［7］Ellis AG, Nice EC, Weinstock J.Hish-performance liquid chromatographic an alysis of the tyrphostin AG1478, a specific inhibitor of the epidermal growth factor receptor tyrosine kinase, in mouse plasma［J］．Chromatogr B Biomed Sci, 2001, 754(1): 193-199.
［8］Busse D, Doughty RS, Ramsey TT, Russell WE, Price JO, Flanagan WM et al. Reversible G1 arrest induced by inhibition of the epidermal growth factor receptor tyrosine kinase requires up-regulation of p27 Kip1 independent of MAPK activity［J］. J Biol Chem, 2000, 275(10): 6987-6995.
［9］Vargaftig BB, Singer M. Leukotrienes mediate part of Ova-induced lung effects in mice via EGFR［J］. Am J Physiol Lung Cell Mol Physiol, 2003, 285(6):L808-L818.