摘要
目的研究表皮生长因子酪氨酸受体抑制剂(EGFR-TKI)——吉非替尼(gefitinib)在丙烯醛诱导气道黏液高分泌中的作用。方法采用丙烯醛诱导气道黏液高分泌建立大鼠模型,将大鼠分为正常对照组(A组,不予以任何干预),模型组(B组,丙烯醛雾化吸入),药物干预组(C、D、E组,在丙烯醛雾化前30 min,分别以10 mg/kg、20 mg/kg、30 mg/kg的吉非替尼灌胃),药物对照组(F组,生理盐水雾化前30 min,以30 mg/kg吉非替尼灌胃),每组6只大鼠。上述处理持续3周后处死实验动物并取其肺组织,分别进行RT-PCR检测黏蛋白MUC5ACmRNA的表达,免疫组化检测气道MUC5AC和EGFR的蛋白表达,阿尔辛蓝-过碘酸雪夫氏染色(AB-PAS)检测杯状细胞数目。结果模型组大鼠肺组织MUC5AC、EGFR表达增强,杯状细胞数增加;吉非替尼对丙烯醛引起的MUC5AC表达、杯状细胞数增加均具有抑制作用,随着浓度的增加,抑制作用加强;吉非替尼对EGFR信号通路中EGFR蛋白表达具有抑制作用。结论丙烯醛活化EGFR使MUC5AC过度表达,吉非替尼通过对EGFR信号通路的调节,在气道黏液高分泌中具有保护作用。
Objective To test the effect of gefinitib, an EGFR-TKI, on airway mucus hypersecretion induced by acrolein in rats. Methods Thirty six rats were randomly divided into six groups, each with six rats. Group A did not get any intervention; group B had airway mucus hypersecretion induced by inhaled acrelein; Gefitinib intervention was given to group C, D, and E, with a dose of 10 mg/kg,20 mg/kg, and 30 mg/kg of gefitnib administered by gavage, respectively, 30 min before exposure to acrolein inhalation; group F served as a control group, with gefitinib (30 mg/kg) administered by gavage 30 min before exposure to saline inhalation. After three weeks, the rats were sacrificed. The lung tissue sections were obtained. The immunohistochemistry and RT-PCR were performed to detect the MUC5AC and its mRNA expression. The EGFR was detected by immunohistochemical staining. The goblet cells were identified with Alician Blue-periodic Acid Schiff (AB-PAS). Results Overexpression of MUC5AC, EGFR and increased goblet cells in the lungs of the rats were found in the rats exposed to acrolein inhalations. Gefitinib intervention inhibited the expression of MUC5AC and the increase of goblet cells induced by acrolein. Gefitinib also reduced the expression of EGFR in the lungs. Conclusion Acrolein increases the expression of MUC5AC through activating EGFR, which indicates that EGFR-TKI such as gefitinib can be useful in the treatment of mucus hypersecretion by regulating the signal transduction pathways of EGFR.
出处
《四川大学学报(医学版)》
CAS
CSCD
北大核心
2008年第2期231-234,共4页
Journal of Sichuan University(Medical Sciences)
基金
国家自然科学基金(批准号30370628)
四川省科技厅科技攻关项目(2006Z09-021)资助