慢性阻塞性肺疾病患者气道上皮水通道5的表达与黏液高分泌

目的 通过检测慢性阻塞性肺疾病（COPD）患者气道上皮水通道5（AQP5）和黏蛋白MUC5AC、黏膜下腺黏蛋白的表达，探讨COPD患者气道黏液高分泌的机制。方法 取2004年华西医院胸外科手术病人离体标本，根据术前检查结果将患者分为轻度COPD组（8例）、中重度COPD组（17例）和对照组（20例），分别用RT-PCR、原位杂交、免疫组化、阿辛兰．PAS染色检测气道上皮细胞AQP5、MUC5AC以及黏蛋白的表达。结果 与正常对照组相比较，COPD组患者黏膜下腺AQP5表达低于对照组（P〈0．01），两组患者肺组织AQP5表达差异无统计学意义（P〉0．05）；中重度COPD组患者黏膜下腺AQP5表达低于轻度COPD组（P〈0．01）。COPD组患者气道上皮MUC5AC表达高于对照组（P〈0．01），中重度COPD组患者气道上皮MUC5AC表达高于轻度COPD组（P〈0．01）；COPD组黏膜下腺分泌黏蛋白较对照组增加（P〈0．01），中重度COPD组患者黏膜下腺分泌黏蛋白表达高于轻度COPD组（P〈0．01）。黏膜下腺AQP5mRNA表达与患者FEV1／FVC、FEW1％pred、V50％pred、V25％pred呈正相关（r分别为0．60，0．60，0．55和0．45，P均〈0．01），AQP5的表达减弱与COPD患者的气道气流受限严重程度有关；与患者气道上皮MUC5ACmRNA表达呈负相关（r=-0．45，P〈0．01）；与黏膜下腺着色面积呈负相关（r=-0．61，P：0．01）。气道上皮MUC5ACmRNA表达与患者FEV1／FVC、FEV1％pred、V50％pred、V25％pred呈负相关（r分别为-0．53，-0．53，-0．48和-0．43，P均〈0．01）；与黏膜下腺黏液着色面积呈正相关（r=0．43，P〈0．05）。结论 COPD患者的黏膜下腺AQPs较对照组表达降低，AQPs可能参与了COPD患者气道黏液分泌的调节。

Aquaporin-5 expression in airway epithelium and its role in airway mucus overproduction in chronic obstructive pulmonary disease

Objective To investigate the relationship of aquaporin-5(AQP_5)and mucus overproduction in the airway of Chinese patients with chronic obstructive pulmonary disease(COPD).Methods Bronchial tissues were isolated from non-cancerous regions of surgical resected specimens due to lung neoplasm in West China Hospital from April to July,2004.25 patients were diagnosed as lung neoplasm with COPD(8 patients with mild COPD,17 patients with moderate and severe COPD)and other 20 were diagnosed as lung neoplasm without COPD as the controls.The expressions of AQP_5,MUC5AC and mucin in bronchial tissues were detected by RT-PCR,in situ hybridization with DIG-labeled RNA probe,immunohistochemical and Alcian blue-periodic acid Schiff(AB-PAS)staining,respectively.Results Compared with the control subjects,a reduced expression of AQP_5 was detected throughout the bronchial tissues in patients with COPD(P<0.01),while no significant difference existed in the lung tissues(P>0.05).Furthermore,an expression of AQP_5 in moderate and severe COPD group was reduced compared with that in mild COPD group.The samples from COPD patients showed a stronger staining for MUC5AC than those in the control subjects(P<0.01)and AB-PAS staining revealed more mucins in COPD patients' submucosal gland compared with that in control subjects(P<0.01).Expressions of MUC5AC and mucins in moderate and severe COPD group were increased compared with that in mild COPD group.Expression levels of AQP_5 mRNA were well correlated with the patients' FEV_1/FVC,FEV_1% predicted,V_ 50 %predicted,V_ 25 %predicted(r=0.60,0.60,0.55,0.45,respectively,all P<0.01),implying decreased expression of the AQP_5 mRNA was related to the severity of airflow obstruction.The expression levels of AQP_5 mRNA were negatively correlated with the expression levels of the MUC5AC mRNA of airway epithelium(r=-0.45,P<0.01)and the PAS-AB stained area of submucosal glands(r=-0.61,P<0.01).Expression levels of the MUC5AC mRNA were negatively correlated with the patients' FEV_1/FVC,FEV_1%predicted,V_ 50 %predicted,V_ 25 %predicted(r=-0.53,-0.53,-0.48,-0.43,respectively,all P<0.01).The expression levels of the MUC5AC mRNA were well correlated with the positively PAS-AB stained area of submucosal gland(r=0.43,P<0.05).WTHZ]Conclusion These results suggest that the suppressed gene expression of AQP_5 may be involved in mucus hypersecretion in the airway of Chinese patients with COPD.