Zhang Zi-Qiang, Song Yuan-Lin, Chen Zhi-Hong, Shen Yao, Bai Chun-Xue
Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.
J Trauma. 2011 Nov;71(5):1305-11. doi: 10.1097/TA.0b013e3182128528.
Aquaporin (AQP) is a membrane protein that facilitates osmotic water transport. Aquaporin 5 (AQP5) expresses at type I alveolar epithelia of apical membrane that confers high osmotic water permeability. Osmosis or stretch challenge in alveoli significantly up-regulates AQP5 expression, which suggests that AQP5 may play a role in the maintenance of epithelia barrier function. Pseudomonas aeruginosa (PA), a leading gram-negative bacterial frequently isolated from ventilation-associated pneumonia patients, disrupts alveolar and airway epithelial cells and subsequently leads to blood dissemination. In this study, we hypothesized that AQP5 might be protective in acute lung injury induced by PA, and deletion of AQP5 might lead to aggravated lung injury.
Lung injury model was induced by intratracheal instillation of PA (1 × 10(6) colony-forming unit) in wild-type and AQP5 knockout mice, 2 hours and 6 hours later, blood and lung lysate were cultured to detect blood dissemination, bronchoalveolar lavage fluid and lung tissue were collected for histology analysis. Lung injury assessment, wet/dry weight ratio, protein leakage, and Evan's blue dye extravasation were evaluated for pulmonary barrier function.
AQP5 deficiency led to increased bacterial blood dissemination and aggravated lung injury during PA infection, and AQP5 deletion also reduced mucin production in lung. Moreover, AQP5 deficiency showed declined activation of mitogen-activated protein kinase and nuclear factor-kappa B pathways in lungs before and after PA infection.
Our data demonstrated that AQP5 plays a protective role in the maintenance of pulmonary barrier function against PA infection.
水通道蛋白（AQP）是一种促进渗透性水转运的膜蛋白。水通道蛋白5（AQP5）表达于Ⅰ型肺泡上皮细胞的顶端膜，赋予其高渗透性水通透性。肺泡中的渗透或拉伸刺激可显著上调AQP5的表达，这表明AQP5可能在维持上皮屏障功能中发挥作用。铜绿假单胞菌（PA）是一种常从呼吸机相关性肺炎患者中分离出的主要革兰氏阴性菌，它会破坏肺泡和气道上皮细胞，随后导致血行播散。在本研究中，我们假设AQP5可能对PA诱导的急性肺损伤具有保护作用，而AQP5的缺失可能导致肺损伤加重。
通过气管内滴注PA（1×10⁶菌落形成单位）在野生型和AQP5基因敲除小鼠中诱导肺损伤模型，2小时和6小时后，培养血液和肺裂解物以检测血行播散，收集支气管肺泡灌洗液和肺组织进行组织学分析。评估肺损伤、湿/干重比、蛋白渗漏和伊文思蓝染料外渗以评价肺屏障功能。
AQP5缺乏导致PA感染期间细菌血行播散增加和肺损伤加重，并且AQP5缺失还降低了肺中粘蛋白的产生。此外，AQP5缺乏显示PA感染前后肺中丝裂原活化蛋白激酶和核因子-κB通路的激活下降。
我们的数据表明AQP5在维持肺屏障功能抵抗PA感染中起保护作用。
