水通道蛋白5在高氧肺损伤中的表达及调节机制

Expression and modulation of aquaporin 5 in hyperoxia-induced lung injury

目的探讨水通道蛋白5(AQP5)在高氧肺损伤中的表达及其地塞米松对AQP5的调节作用。方法2周左右Wistar大鼠64只,按随机数字表法分为空气对照组、高氧暴露3、7、14d组和相应的地塞米松干预组。高氧暴露组置于常压氧仓中(O2体积分数≥95%);空气对照组置于同室常压空气中(O2体积分数为21%);各地塞米松干预组在暴露于空气或高氧的同时,经腹腔注射地塞米松5mg·kg-1·d-1,连续3d。采用逆转录聚合酶链反应(RT PCR)和免疫组化方法观察AQP5的mRNA表达和分布变化,并与地塞米松干预后进行比较分析。结果AQP5主要表达在肺泡型上皮细胞及气道分泌上皮顶质膜;与空气对照组相比,高氧暴露不同时间后,AQP5特异性表达部位保持不变,但随暴露时间延长,AQP5表达呈逐渐减弱趋势,高氧暴露3、7和14d,AQP5mRNA较空气对照组均降低(P均<0.05)。与同期高氧暴露组比较,地塞米松干预后不同时间点AQP5mRNA表达均无明显变化(P均>0.05)。结论高氧肺损伤时AQP5表达降低,可能是高氧肺损伤肺水肿形成的原因之一;而未见地塞米松对高氧肺损伤AQP5的表达有调节作用。

Objective To explore the expression and the modulation of aquaporin 5 （AQP5） in hyperoxia-induced lung injury. Methods Sixty-four Wistar rats of 2 weeks old, were randomly assigned to following groups （n = 8） ： air group, hyperoxia 3, 7, 14 days groups, air ＋ dexamethasone （Dex）, hyperoxia 3, 7, 14 days ＋ Dex groups. The rats were kept in oxygen chamber at normal pressure （O2≥95% ） in hyperoxia groups, and in normal pressure air （O2= 21%） in room-air group, and the rats in Dex groups were injected with Dex （5 mg· kg^-1· d^-1） intraperitoneally for 3 consecutive days in room-air or hyperoxia exposure. The expression of AQP5 mRNA level and the location were detected by reverse transcription-polymerase chain reaction and immunohistochemistry respectively. Results AQP5 was strongly labeled in alveolar epithelial type 1 cells, and was also expressed in the secretory epithelium plasma membrane in the airway. The location of AQP5 in hyperoxia groups was not changed, but the expression of AQP5 mRNA had a notable gradual decline when the time of hyperoxia exposure was prolonged, compared to control group（all P〈0.05）. There was no difference in AQP5 mRNA level between hyperoxia groups and hyperoxia ＋ Dex groups at different time points （all P〈0.05）. Conclusion The significant decrease in AQP5 may be an important factor of pulmonary edema formation in hyperoxia-induced lung injury. Dex does not have effect on modulating the AQP5 expression in acute lung injury.