Wang Ke, Feng Yu-Ling, Wen Fu-Qiang, Chen Xue-Rong, Ou Xue-Mei, Xu Dan, Yang Jie, Deng Zhi-Pin
Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, and Department of Respiratory Medicine, West China Hospital of Sichuan University, Chengdu 610041, China.
Chin Med J (Engl). 2007 Jun 20;120(12):1051-7.
Chronic obstructive pulmonary disease (COPD) is usually complicated with mucus overproduction in airway. Recently the increased expression of the human calcium-activated chloride channel 1 (CaCC(1)) was found to play an important role in mucus overproduction in the asthmatic airways. To investigate the relationship of CaCC(1) and mucus overproduction in the airway of Chinese patients with COPD, the expressions of CaCC(1), MUC5AC and mucus in bronchial tissues were examined.
Bronchial tissues were obtained from fiberoptic bronchoscopy and bronchial biopsy in West China Hospital from April to July in 2004. Twenty-five patients were diagnosed as the patients with COPD overproduction, and other 20 were the control subjects. The expressions of CaCC(1), MUC5AC and mucin in bronchial tissues were detected by reverse transcriptase-polymerase chain reaction (RT-PCR), in situ hybridization with digoxigenin (DIG)-labeled RNA probe, immunohistochemical and alcian blue-periodic acid Schiff (AB-PAS) staining, respectively.
Compared with the control group, the stronger expressions of CaCC(1) were further detected throughout the bronchial tissues from patients with COPD (P < 0.01). Furthermore, the stronger expressions of the CaCC(1) mRNA were related to the severity of airflow obstruction. Samples from COPD showed a stronger staining for MUC5AC than those in control subjects (P < 0.01) and AB-PAS staining revealed more mucins in COPD patients' submucosal gland comparing with that in control subjects (P < 0.01). Expression levels of the CaCC(1) mRNA were respectively negatively correlated with the patients' forced expiratory volume in one second (FEV(1))/forced vital capacity (FVC) data, FEV(1)% predicted data, V(50)% predicted data, V(25)% predicted data (r = -0.43, r = -0.43, r = -0.35, r = -0.36, P < 0.01, P < 0.01, P < 0.05, P < 0.05). While the expression levels of the CaCC(1) mRNA were well correlated with the expression levels of the MUC5AC mRNA of airway epithelium and the PAS-AB stained area of submucosal glands (r = 0.39, r = 0.46, P < 0.05, P < 0.01). Expression levels of the MUC5AC mRNA were negatively correlated with the patients' FEV(1)/FVC data (P = 0.01), FEV(1)% pred data (P = 0.01), V(50)% predicted data, V(25)% predicted data (r = -0.53, r = -0.53, r = -0.48, r = -0.43, P < 0.01, P < 0.01, P < 0.01, P < 0.01). While the expression levels of the MUC5AC mRNA were well correlated with the positively PAS-AB stained area of submucosal gland (P < 0.05), and the correlation coefficients were 0.43.
These results suggest that the stronger gene expression of CaCC(1) exists, complicated with mucus overproduction in the airway of Chinese patients with COPD.
慢性阻塞性肺疾病（COPD）通常伴有气道黏液过度分泌。最近发现人类钙激活氯离子通道1（CaCC(1)）表达增加在哮喘气道黏液过度分泌中起重要作用。为研究中国COPD患者气道中CaCC(1)与黏液过度分泌的关系，检测了支气管组织中CaCC(1)、MUC5AC和黏液的表达。
2004年4月至7月从华西医院通过纤维支气管镜检查和支气管活检获取支气管组织。25例患者被诊断为COPD黏液过度分泌患者，另外20例为对照受试者。分别采用逆转录聚合酶链反应（RT-PCR）、地高辛（DIG）标记RNA探针原位杂交、免疫组化和阿尔辛蓝-过碘酸希夫（AB-PAS）染色检测支气管组织中CaCC(1)、MUC5AC和黏蛋白的表达。
与对照组相比，COPD患者整个支气管组织中CaCC(1)表达更强（P < 0.01）。此外，CaCC(1) mRNA表达增强与气流阻塞严重程度相关。COPD样本中MUC5AC染色比对照组更强（P < 0.01），AB-PAS染色显示COPD患者黏膜下腺中的黏蛋白比对照组更多（P < 0.01）。CaCC(1) mRNA表达水平分别与患者一秒用力呼气容积（FEV(1)）/用力肺活量（FVC）数据、FEV(1)%预计值数据、V(50)%预计值数据、V(25)%预计值数据呈负相关（r = -0.43，r = -0.43，r = -0.35，r = -0.36，P < 0.01，P < 0.01，P < 0.05，P < 0.05）。而CaCC(1) mRNA表达水平与气道上皮MUC5AC mRNA表达水平及黏膜下腺PAS-AB染色面积呈良好相关性（r = 0.39，r = 0.46，P < 0.05，P < 0.01）。MUC5AC mRNA表达水平与患者FEV(1)/FVC数据（P = 0.01）、FEV(1)%预计值数据（P = 0.01）、V(50)%预计值数据、V(25)%预计值数据呈负相关（r = -0.53，r = -0.53，r = -0.48，r = -0.43，P < 0.01，P < 0.01，P < 0.
