哮喘患者气道上皮钙激活的氯离子通道1表达增加与黏液高分泌

目的　通过检测哮喘患者气道上皮钙激活的氯离子通道 1 (CaCC1 )和黏蛋白MUC5AC、黏膜下腺黏蛋白的表达情况 ,探讨哮喘患者气道黏液高分泌的机制。方法　取 2 0 0 4年华西医院胸外科手术病人离体标本 ,其中哮喘患者 6例 ,非哮喘患者 1 0例作为对照。分别用原位杂交、免疫组化、阿辛兰 PAS染色检测气道上皮细胞CaCC1 、MUC5AC及黏蛋白的表达。结果　与正常对照组比较 ,哮喘组患者气道上皮CaCC1 、MUC5AC表达细胞较对照组增加 ,强度增强 (P值分别为0 .0 1和 0 . 0 4 ) ;哮喘组和对照组气道上皮的杯状细胞均有黏蛋白的分泌 ,哮喘组分泌黏蛋白的杯状细胞较对照组增加 (P =0 . 0 1 ) ;哮喘组黏膜下腺较对照组分泌黏蛋白增加 (P <0 . 0 5 )。哮喘组气道上皮CaCC1 表达增加与MUC5AC表达增加呈正相关 (P =0 . 0 1 ,r=0 . 76 5 )。哮喘组气道上皮CaCC1表达增加与该组患者气道上皮黏蛋白阳性细胞百分比增加呈正相关 (P =0 .0 1 ,r =0 . 75 7) ;哮喘组气道上皮CaCC1 表达增加与黏膜下腺光密度、着色面积、光密度×着色面积增加均呈正相关 (P值分别为 0 . 0 3、0 . 0 2和 0. 0 1 ,r分别为 0 . 5 5 4、0 . 5 94和 0 . 6 1 9)。结论　CaCC1 在哮喘患者气道上皮表达增加 ,可能与哮喘患者的气道黏液高分泌密切相关。

Increased expression of the human calcium-activatied chloride channel 1 and mucus hypersecretion in the asthmatic airway

Objective To investigate the expression levels of calcium-activated chloride channel 1 (CaCC 1),MUC5AC and mucin in bronchial tissues to explore the mechanism of mucus hypersecretion in asthma.Methods Lung tissues were obtained from patients with lung neoplasm after surgical operation in West China Hospital from April to July in 2004.Six patients diagnosed as moderate asthma before operation and ten patients without asthma were enrolled.All subjects were nonsmokers and had no respiratory tract infections within 2 weeks before operation.The expressions of CaCC 1,MUC5AC and mucin in bronchial tissues were examined by situ hybridized with DIG-labeled RNA probes,histochemical analysis and Alcian blue-periodic acid Schiff (PAS) staining.Results In situ hybridization,overexpression of CaCC 1 mRNA was detected throughout the bronchial tissues from patients with asthma compared to control subjects (P=0.01).Histochemical analysis demonstrated stonger staining of CaCC 1 in the samples from asthmatics than that from control subjects (P=0.04).Alcian blue-PAS staining revealed more mucin and goblet cells in the asthmatic bronchial epithelial and submucosal gland compared to control subjects (P<0.05).The increased expression of CaCC 1 in asthma subjects were well correlated with the expression of MUC5AC protein and Alcian blue-PAS staining (P=0.01,P=0.01,P=0.02) in asthma patients.Conclusion CaCC 1 may play an important role in mucus overproduction in asthmatic airway.