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

摘要:

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。

Abstract:

OBJECTIVE: Aquaporin (AQP) is a group of cell membrane transporting proteins. The study was designed to investigate the changes of AQP_1 and AQP_5 in the lung tissue under hyperoxia and their roles in pulmonary edema. METHODS: Two hundred newborn rats were randomized into different oxygen concentrations exposure: FiO_2=0.80 (Experimental group 1), FiO_2=0.60 (Experimental group 2), FiO_2=0.40 (Experimental group 3) and FiO_2=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_1 and AQP_5 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 AQP_1 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_1 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 AQP_5 in the experimental groups were reduced compared with that in the Air control group 3 days after hyperoxia-exposure and the decrease of AQP_5 expression was associated with duration of hyperoxia-exposure. The comparison among three experimental groups showed that the decrease of AQP_1 and AQP_5 expressions was associated with the concentration of hyperoxia-exposure. CONSUIONS: The expressions of AQP_1 and AQP_5 decreased in hyperoxia-induced lung injury and correlated with the severity of pulmonary edema.