高压氧预处理对急性高原肺水肿大鼠肺水通道蛋白1和水通道蛋白5影响的实验研究

摘要

目的 评价高压氧预处理预防急性高原肺水肿的作用.方法 健康雄性Wistar大鼠32只,随机数字表法分为3组:正常对照(normal,N)组8只,高压氧预处理(HBO-PC)组12只,高原肺水肿(HAPE)组12只.建立急性高原肺水肿大鼠模型.应用Western-blot技术检测各组肺组织水通道蛋白1(AQP1)、水通道蛋白5(AQP5)水平的变化;光学显微镜下观察动物肺泡间质的水肿、炎性细胞浸润以及出血情况,并进行病理损伤评分.结果(1)HAPE组AQP1、AQP5蛋白条带灰度(0.5335±0.0869、0.6015±0.1372)与N组相比均明显降低(P＜0.01);HBO-PC组AQP1、AQP5蛋白条带灰度(0.7342±0.1937、0.7325±0.1255)与HAPE组相比均升高(P＜0.01,P＜0.05).(2)HAPE组与N组相比,肺组织损伤程度明显加重,肺组织病理评分明显升高(P＜0.01);HBO-PC组与HAPE组相比,肺组织损伤程度明显减轻,肺组织病理评分明显降低(P＜0.01).(3)肺组织损伤与肺AQP1、AQP5蛋白表达之间均具有相关性(rAQP=-0.774,rAQP5=-0.661,P＜0.01).结论(1)发生HAPE时,肺内AQP1、AQP5蛋白表达降低,AQP1、AQP5的下调是导致HAPE引起肺损伤的机理之一,且AQP1、AQP5的蛋白表达水平与肺损伤的严重程度呈负相关.(2)高压氧预处理能够减轻HAPE程度,对HAPE具有预防作用,其可能机制之一是高压氧通过上调AQP1和AQP5的蛋白表达而发挥作用.%Objective To evaluate the effect of hyperbaric oxygen(HBO)on prevention of acute high altitude pulmonary edema.Methods Thirty-two healthy male Wistar rats were randomly divided into 3 different groups:the control group(N,n=8),the HBO preconditioning group(HBO-PC,n=12)and the high altitude pulmonary edema group(HAPE,n=12).An animal model of acute high altitude pulmonary edema was developed.Changes in the expressions of aquaporins 1(AQP1)and aquaporins 5(AQP5)were detected with Western blot.Alveolar and interstitial edema,inflammatory cell infiltration and hemorrhage were observed with microscopy.In the meantime,pathological scores were assessed accordingly.Results(1)The expressions of AQP1(0.5335±0.0869)and AQP5(0.6015±0.1372)in the HAPE group were significantly lower than those in the control group(P＜0.01,P＜0.01),while the expressions of AQP1(0.7342±0.1937)and AQP5(0.7325±0.1255)in the HBO-PC group were significantly higher than those in the HAPE group(P＜0.01,P＜0.05).(2)Pulmonary injury in the HAPE group was obviously worse than that in the control group(P＜0.01),and that pulmonary pathohistological scores of the HBO-PC group were significantly higher than those of the HAPE group(P＜0.01).When compared with that of the HAPE group,pulmonary injury in the HBO-PC group was obviously lighter and pulmonary pathohistological scores were also significantly lower(P＜0.01).(3)Pulmonary injury was closely correlated with the expressions of AQP1 and AQP5(rAQp1=-0.774;rAQP5=-0.661,P＜0.01).Conclusions(1)In case of HAPE,lower expression and down regulation of AQP1 and AQP5 at protein level was one of the mechanisms involved in pulmonary injury.The expression levels of AQP1 and AQP5 were negatively correlated with the seriousness of pulmonary injury.(2)preconditioning could decrease the seriousness of HAPE and seemed to have some preventive effect on HAPE.One of the mechanisms in which HBO may be involved possibly lies in the up-regulation of AQP1 and AQP5.