表皮生长因子受体信号通路对慢性烟曲霉暴露哮喘大鼠气道重塑的影响  

Effects of epidermal growth factor receptor signal pathway on the airway remodeling induced by chronic Aspergillus fumigatus exposure in rats with asthma

作　　者：汪泽[1] 高艳艳[2] 刘永全[2] 高福生[2] 

机构地区：[1]潍坊医学院,山东潍坊261053 [2]潍坊医学院附属医院呼吸内科,山东潍坊261031

出　　处：《中国医药导报》2015年第12期4-7,F0003,共5页China Medical Herald

基　　金：山东省自然科学基金资助项目(编号ZR2012HM094)

摘　　要：目的探讨表皮生长因子受体(EGFR)信号通路对慢性烟曲霉暴露哮喘大鼠气道重塑的影响。方法将30只Wistar雄性大鼠随机分为3组:A组(慢性哮喘大鼠),以卵清蛋白(OVA)系统致敏和反复激发方法制备大鼠慢性哮喘模型;B组(慢性哮喘大鼠+烟曲霉孢子吸入):慢性哮喘大鼠经鼻吸入100μL烟曲霉孢子悬液(含1×104cfu/m L孢子),每周2次;C组[AG1478(EGFR抑制剂)预处理慢性哮喘大鼠+烟曲霉孢子吸入]:慢性哮喘大鼠经鼻吸入AG1478 3 mg/kg,每周1次,同时经鼻吸入100μL烟曲霉孢子悬液,每周2次。肺组织切片行苏木精-伊红(HE)、过碘酸希夫(PAS)、Masson三色染色,病理图像形态学测定分析,观察各组大鼠气道上皮细胞损伤脱落、杯状细胞增生及上皮下纤维化程度。免疫组化检测各组大鼠气道黏蛋白MUC5AC及气道上皮EGFR的表达。结果 B组大鼠气道上皮损伤脱落[(28.50±7.50)%]、杯状细胞增生[(36.38±9.21)%]及上皮下胶原纤维沉积[(56.55±15.38)%]均高于A组[(6.34±1.81)%、(12.55±3.25)%、(18.23±5.21)%](P<0.01),C组上述指标[(7.32±2.11)%、(10.26±3.12)%、(16.34±4.25)%]与A组比较差异无统计学意义(P>0.05);B组大鼠气道上皮细胞EGFR的表达水平(IOD值)(165±21)明显高于A组(56±18)(P<0.01),B组和C组(155±12)大鼠间差异无统计学意义(P>0.05);B组大鼠气道上皮MUC5AC的表达水平(IOD值)(891±80)明显高于A组(212±46)(P<0.01),C组(198±39)和A组大鼠间差异无统计学意义(P>0.05)。结论慢性烟曲霉暴露使哮喘大鼠气道上皮受损、杯状细胞增生、气道上皮下纤维化加重、上皮EGFR表达增加;应用AG1478抑制EGFR酪氨酸酶磷酸化可减轻哮喘大鼠气道杯状细胞增生及气道上皮下纤维化,下调气道黏蛋白MUC5AC的表达。表皮生长因子受体可能参与慢性烟曲霉暴露诱发的哮喘大鼠气道重塑。Objective To investigate the effects of epidermal growth factor receptor （EGFR） signal pathway on the air-way remodeling induced by chronic Aspergillus fumigatus （A. fumigatus） exposure in rats with asthma. Methods 30 male Wistar rats were randomly divided into 3 groups. Rats in group A were sensitized and challenged with ovalbumin （OVA） to set up chronic asthma model. Chronic asthma rats in group B were given intranasal A . fumigate s spores inhalation twice a week for 5 weeks. Chronic asthma rats in group C were given intranasal EGFR inhibitor AG1478 inhalation once a week prior to A . fumigate s spores inhalation for 5 weeks. Lung sections were stalned with hematoxylin and eosin （HE）, periodic acid Schiff （PAS）, and Masson trichrome, and the images were analyzed morphometrically to evaluate the alrway epithelial detachment, goblet cell hyperplasia and subepithelial collagen deposition in 3 groups of rats. The expression of MUC5AC and EGFR in the alrways was detected and analyzed by immunohistochemistry. Results The alrway epithelial detachment [（28.50±7.50）%], goblet cell hyperplasia [（36.38±9.21）%] and subepithelial collagen deposition [（56.55±15.38）%] in group B were all higher than those in group A [（6.34±1.81）%, （12.55±3.25）% and （18.23±5.21）%] （P〈0.01）. No differences were found in above indexes between group C [（7.32±2.11）%, （10.26±3.12）%and （16.34±4.25）%] and group A （P〉0.05）. The expression of EGFR in the alrways （IOD values） in group B （165±21） was higher than that in group A （56±18） （P〈0.01）, no difference was found between group B and group C （155±12） （P〉0.05）. The expression of MUC5AC in the alrways （IOD values） in group B （891±80） was higher than that in group A （212±46） （P〈 0.01）. No difference was found between group C （198±39） and group A （P〉0.05）. Conclusion Chronic A. fumigates exposure induced aggravation of alrway epithelial detachment, goblet cell hyper

关 键 词：表皮生长因子受体 AG1478 烟曲霉 支气管哮喘 气道重构 

分 类 号：R562.25[医药卫生—呼吸系统]