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表皮生长因子受体对哮喘小鼠气道重塑的影响及其机制

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

作者信息

Li Xiao-Hui, Luan Bin

机构信息

Department of Pediatrics, Third Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, China.

出版信息

Zhongguo Dang Dai Er Ke Za Zhi. 2010 Feb;12(2):137-40.

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.

摘要

目的

探讨哮喘小鼠气道重塑与表皮生长因子受体(EGFR)和肝素结合表皮生长因子样生长因子(HB-EGF)水平的关系,以及EGFR酪氨酸激酶抑制剂(AG1478)对气道重塑的影响。

方法

将24只雄性BALB/c小鼠随机分为三组:正常对照组、哮喘组、AG1478治疗组。用卵清蛋白(OVA)对小鼠进行致敏和激发,制备哮喘小鼠模型。在Masson染色的肺切片中测定胶原沉积。采用过碘酸希夫(PAS)染色观察杯状细胞的增殖情况。用免疫组织化学法测定HB-EGF的蛋白表达。用逆转录聚合酶链反应(RT-PCR)法测定HB-EGF和EGFR的mRNA表达。

结果

哮喘组出现气道重塑的特征性改变。哮喘组支气管上皮细胞中HB-EGF和EGFR的表达明显高于正常对照组。与哮喘组相比,AG1478治疗组炎症反应减轻,胶原沉积和杯状细胞增殖减少,EGFR和HB-EGF表达降低。

结论

EGFR酪氨酸激酶抑制剂(AG1478)通过抑制EGFR和HB-EGF表达及EGFR信号通路,改善哮喘小鼠气道重塑的进程。

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