水通道蛋白1,5与新生鼠高氧肺损伤肺水肿的关系研究

Relationship between expression of aquaporin-1,5 and pulmonary edema in hyperoxia-induced lung injury in newborn rats

目的水通道蛋白(aquaporin,AQP)是新近发现的一组与水通透性有关的细胞膜转运蛋白,该文旨在探讨高氧损伤状态下,肺组织内AQP1,AQP5的动态变化规律及其在肺水肿中的作用。方法新生鼠200只,依据吸氧浓度(F iO2)分组:实验组1(F iO2=0.8)、实验组2(F iO2=0.6)、实验组3(F iO2=0.4)、空气对照组(F iO2=0.21)。每组分别于实验后1,3,5,7,14 d行AQP1、AQP5W estern印迹检测,同时检测肺湿/干重比值(wet/dry we ight ratio,W/D),BALF中蛋白含量。结果高氧各组肺W/D比值、BALF中蛋白含量与空气组相比均显著增加,并随吸氧浓度、暴露时间的增加而增加。实验组AQP1第3天表达开始降低,第5天,第7天明显降低(P<0.05),第14天有所恢复。实验组AQP5表达低于对照组,第1,3天呈稍高表达,以后随日龄增加逐渐降低(P<0.05)。总趋势上AQP1,AQP5的表达在实验组3、实验组2、实验组1依次降低。结论AQP1,AQP5在高氧肺损伤时表达降低,并与肺水肿的严重程度相关。

Objective Aquaporin （AQP） is a group of cell membrane transporting proteins. The study was designed to investigate the changes of AQP, and AQP5 in the lung tissue under hyperoxia and their roles in pulmonary edema. Methods Two hundred newborn rats were randomized into different oxygen concentrations exposure： FiO2=0. 80 （Experimental group 1 ）, FiO2=0.60 （Experimental group 2 ）, FiO2=0.40 （Experimental group 3 ） and FiO2=0. 21 （ Air control group）. Rats were sacrificed at 1, 3, 5, 7 and 14 days after the beginning of experiment （ 10 rats each time point）. The expressions of AQP, and AQP5 were examined by Western Blot. The ratio of lung wet weight to lung dry weight （wet-to-dry weight ratio, W/D）, and the protein content in bronchoalveolar lavage fluid （BALF） were measured. Results Compared with the Air control group, the W/D ratio and the protein content in BALF in the three experiment groups increased significantly and the increased extent was positively related to the duration and the oxygen concentration of hyperoxia-exposure. The expression of AQP1 in the experimental groups began to decrease at the 3rd day and significant differences were found at the 5th and the 7th days after hyperoxia-exposure compared with that in the Air control group （ P〈0.05 ）. The AQP, expression was restored somewhat at the 14th day after hyperoxia-exposure, but it was still lower in the Experimental groups 1 and 2 than that in the Air control group （ P 〈 0.05 ）. The expression of AQP5 in the experimental groups were reduced compared with that in the Air control group 3 days after hyperoxia-exposure and the decrease of AQP5 expression was associated with duration of hyperoxia-exposure. The comparison among three experimental groups showed that the decrease of AQP, and AQP5 expressions was associated with the concentration of hyperoxia-exposure. Conclusions The expressions of AQP, and AQP5 decreased in hyperoxia-induced lung injury and correlated with the severity of pulmonary edema.