表皮生长因子受体和黏蛋白在慢性阻塞性肺疾病气道中的表达及意义

Expression of epidermal growth factor receptor and MUC5AC on human airway with chronic obstructive pulmonary disease

目的 检测表皮生长因子受体 (EGFR)及黏蛋白 5AC(MUC5AC)在外周气道中的表达 ,确定小气道EGFR表达与黏蛋白合成的关系。方法 肺组织标本取自 38例肺癌手术患者 ,于远离病灶处取材 ,按照基础疾病和吸烟史分为慢性阻塞性肺疾病 (COPD)组 16例、吸烟组 10例、对照组 12名 ,用免疫组化和Westernblot方法研究外周小气道EGFR和MUC5AC蛋白表达。结果 吸烟组和COPD组EGFR蛋白表达较高 ,吸光度 (A)值分别为 4 89± 1 89、4 6 2± 1 6 5 ,较对照组 (2 0 1± 1 0 2 )显著增高 (q′ =6 ,P <0 0 1)。吸烟组和COPD组EGFR主要表达在基底细胞 ,阳性百分率分别为 5 2 1%± 13 5 %、4 2 9%± 14 2 % ,比对照组基底细胞阳性百分率 (2 3 7%± 9 5 % )显著增高 (P <0 0 1) ;吸烟组和COPD组EGFR杯状细胞阳性百分率分别为 2 1 9%± 9 7%、2 1 1%± 8 6 % ,比对照组杯状细胞阳性百分率 (71 1%± 14 3% )显著降低 (P <0 0 1)。吸烟组和COPD组EGFR表达量及定位均无显著差异 (P均 >0 0 5 )。在所有研究对象中 ,EGFR阳性区域和MUC5AC阳性区域呈正相关 (r =0 8774 ,P <0 0 0 1)。结论 EGFR活化参与了COPD患者气道上皮黏蛋白表达。

Objective To determine the relationship between epidermal growth factor receptor(EGFR) expression and mucin 5AC(MUC5AC) synthesis in human airways with chronic obstructive pulmonary disease(COPD). Methods Lung specimens were obtained from 38 patients who were undergoing lobectomy,and the samples were taken from areas remote to the lesion. EGFR and MUC5AC protein expression were examined using immunohistochemical analysis and Western blot in peripheral airways(less than 2 mm in diameter) from 16 subjects with COPD,10 subjects with a history of more than 30 pack-year smoking and 12 nonsmokers or exsmokers(0-10 pack-year smoker). Results Weak EGFR protein signals were detected in the lungs of the controls(2.01±1.02) in comparison with stronger signal in the COPD patients(4.62±1.65,P<0.01) and the smokers(4.89±1.89,P<0.01). EGFR immunoreactivity was observed mainly in goblet cells in the controls,the percentage of positive cell being 71.1%±14.3%,which was higher than those in COPD(21.1%±8.6%) or in the smoker(21.9%±9.7%) airways. In contrast,COPD or smoker airways showed more expression of EGFR which expressed mainly in basal cells(42.9%±14.2%,52.1%±13.5%,respectively) than that in the control airways(23.7%±9.5%,P<0.01). However there was no significant differences in EGFR expression and location in peripheral airways between COPD patients and smokers(P>0.05). There was significant positive correlation between EGFR immunoreactivity and the area of the MUC5AC positive staining in all subjects(r=0.877 4,P<0.001). Conclusion It is suggested that EGFR activation is involved in mucin expression in COPD airways.