中国医药导报
中國醫藥導報
중국의약도보
CHINA MEDICAL HERALD
2015年
12期
4-7
,共4页
汪泽%高艳艳%刘永全%高福生
汪澤%高豔豔%劉永全%高福生
왕택%고염염%류영전%고복생
表皮生长因子受体%AG1478%烟曲霉%支气管哮喘%气道重构
錶皮生長因子受體%AG1478%煙麯黴%支氣管哮喘%氣道重構
표피생장인자수체%AG1478%연곡매%지기관효천%기도중구
Epidermal growth factor receptor%AG1478%Asthma%A spergillus fumigatus%Airway remodeling
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组院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）院慢性哮喘大鼠经鼻吸入100μL烟曲霉孢子悬液（含1×104 cfu/mL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]院慢性哮喘大鼠经鼻吸入AG14783 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-×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。
目的：探討錶皮生長因子受體（EGFR）信號通路對慢性煙麯黴暴露哮喘大鼠氣道重塑的影響。方法將30隻Wistar雄性大鼠隨機分為3組院A組（慢性哮喘大鼠），以卵清蛋白（OVA）繫統緻敏和反複激髮方法製備大鼠慢性哮喘模型；B組（慢性哮喘大鼠+煙麯黴孢子吸入）院慢性哮喘大鼠經鼻吸入100μL煙麯黴孢子懸液（含1×104 cfu/mL孢子），每週2次；C組[AG1478（EGFR抑製劑）預處理慢性哮喘大鼠+煙麯黴孢子吸入]院慢性哮喘大鼠經鼻吸入AG14783 mg/kg，每週1次，同時經鼻吸入100μL煙麯黴孢子懸液，每週2次。肺組織切片行囌木精-×紅（HE）、過碘痠希伕（PAS）、Masson三色染色，病理圖像形態學測定分析，觀察各組大鼠氣道上皮細胞損傷脫落、杯狀細胞增生及上皮下纖維化程度。免疫組化檢測各組大鼠氣道黏蛋白MUC5AC及氣道上皮EGFR的錶達。結果 B組大鼠氣道上皮損傷脫落[（28.50±7.50）%]、杯狀細胞增生[（36.38±9.21）%]及上皮下膠原纖維沉積[（56.55±15.38）%]均高于A組[（6.34±1.81）%、（12.55±3.25）%、（18.23±5.21）%]（P<0.01），C組上述指標[（7.32±2.11）%、（10.26±3.12）%、（16.34±4.25）%]與A組比較差異無統計學意義（P>0.05）；B組大鼠氣道上皮細胞EGFR的錶達水平（IOD值）（165±21）明顯高于A組（56±18）（P<0.01），B組和C組（155±12）大鼠間差異無統計學意義（P>0.05）；B組大鼠氣道上皮MUC5AC的錶達水平（IOD值）（891±80）明顯高于A組（212±46）（P<0.01），C組（198±39）和A組大鼠間差異無統計學意義（P>0.05）。結論慢性煙麯黴暴露使哮喘大鼠氣道上皮受損、杯狀細胞增生、氣道上皮下纖維化加重、上皮EGFR錶達增加；應用AG1478抑製EGFR酪氨痠酶燐痠化可減輕哮喘大鼠氣道杯狀細胞增生及氣道上皮下纖維化，下調氣道黏蛋白MUC5AC的錶達。錶皮生長因子受體可能參與慢性煙麯黴暴露誘髮的哮喘大鼠氣道重塑。
목적：탐토표피생장인자수체（EGFR）신호통로대만성연곡매폭로효천대서기도중소적영향。방법장30지Wistar웅성대서수궤분위3조원A조（만성효천대서），이란청단백（OVA）계통치민화반복격발방법제비대서만성효천모형；B조（만성효천대서+연곡매포자흡입）원만성효천대서경비흡입100μL연곡매포자현액（함1×104 cfu/mL포자），매주2차；C조[AG1478（EGFR억제제）예처리만성효천대서+연곡매포자흡입]원만성효천대서경비흡입AG14783 mg/kg，매주1차，동시경비흡입100μL연곡매포자현액，매주2차。폐조직절편행소목정-×홍（HE）、과전산희부（PAS）、Masson삼색염색，병리도상형태학측정분석，관찰각조대서기도상피세포손상탈락、배상세포증생급상피하섬유화정도。면역조화검측각조대서기도점단백MUC5AC급기도상피EGFR적표체。결과 B조대서기도상피손상탈락[（28.50±7.50）%]、배상세포증생[（36.38±9.21）%]급상피하효원섬유침적[（56.55±15.38）%]균고우A조[（6.34±1.81）%、（12.55±3.25）%、（18.23±5.21）%]（P<0.01），C조상술지표[（7.32±2.11）%、（10.26±3.12）%、（16.34±4.25）%]여A조비교차이무통계학의의（P>0.05）；B조대서기도상피세포EGFR적표체수평（IOD치）（165±21）명현고우A조（56±18）（P<0.01），B조화C조（155±12）대서간차이무통계학의의（P>0.05）；B조대서기도상피MUC5AC적표체수평（IOD치）（891±80）명현고우A조（212±46）（P<0.01），C조（198±39）화A조대서간차이무통계학의의（P>0.05）。결론만성연곡매폭로사효천대서기도상피수손、배상세포증생、기도상피하섬유화가중、상피EGFR표체증가；응용AG1478억제EGFR락안산매린산화가감경효천대서기도배상세포증생급기도상피하섬유화，하조기도점단백MUC5AC적표체。표피생장인자수체가능삼여만성연곡매폭로유발적효천대서기도중소。
Objective To investigate the effects of epidermal growth factor receptor (EGFR) signal pathway on the alr-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 in-halation twice a week for 5 weeks. Chronic asthma rats in group C were given intranasal EGFR inhibitor AG1478 in-halation 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 e-valuate 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. Re-sults The alrway epithelial detachment [(28.50±7.50)%], goblet cell hyperplasia [(36.38±9.21)%] and subepithelial col-lagen 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 ex-pression 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 aggrava-tion of alrway epithelial detachment, goblet cell hyperplasia and subepithelial collagen deposition, and upregulated MUC5AC and EGFR expression in chronic asthma rats. EGFR inhibitor AG1478 inhalation downregulated alrway ep-ithelial detachment, goblet cell hyperplasia, subepithelial collagen deposition and MUC5AC expression in chronic asth-ma rats. EGFR signal pathway may play a role in the alrway remodeling induced by chronic A . fumigate s exposure in chronic asthma rats.
