水通道蛋白-1与大鼠急性一氧化碳中毒性脑病的关系  

Expression of aquaporin 1 is changed on the brain tissue in rat after acute carbon monoxide poisoning

作　　者：李金兰 刘群会 曹学兵[2] 贾敏 谭明会 聂淑科 陈贵勤 LI Jin-lan;LIU Qun-hui;CAO Xue-bing(Department of Neurology,Enshi Tufia and Miao Autonomous Prefecture Center Hospital,Eushi 445000,China)

机构地区：[1]恩施土家族苗族自治州中心医院(武汉大学恩施临床学院)神经内科,445000 [2]华中科技大学附属协和医院神经内科 [3]武汉大学人民医院神经内科Ⅰ科

出　　处：《临床神经病学杂志》2018年第6期456-461,共6页Journal of Clinical Neurology

基　　金：湖北省自然科学基金(2014CFB424)

摘　　要：目的观察急性一氧化碳(CO)中毒后大鼠脑组织水通道蛋白1(AQP1)的表达,探讨AQP1与急性CO中毒性脑病发生的相关性及其作用机制。方法将112只健康雄性SD大鼠随机分为空白对照组(BC组,n=8)、急性CO中毒组(CO组,n=8)。腹腔注射CO或空气制备大鼠模型。分别于大鼠造模后3 h、6 h、12 h、24 h、48 h、72 h、7 d取大鼠脑组织额叶皮质,利用免疫印迹法检测AQP1、胶质纤维酸性蛋白(GFAP)、p38丝裂原激活蛋白激酶(p38 MAPK)、磷酸化p38 MAPK(p-p38 MAPK)的表达变化。免疫组化染色检测大鼠额叶皮质AQP1蛋白的表达。结果 Western blotting法显示,在6 h、12 h、24 h时,大鼠脑皮质CO组的AQP1表达量与BC组比较,差异均有统计学意义(均P <0. 05),大鼠在CO中毒后24 h脑皮质AQP1的表达量最多。CO组大鼠脑皮质在6 h、12 h、24 h时的GFAP表达量与BC组比较,差异均有统计学意义(均P <0. 05),在24 h CO组大鼠GFAP的表达达到峰值。CO组在造模后3 h、6 h、12 h、24 h、48 h、72 h、7 d各个观察时间点的p38 MAPK表达量与BC组比较均无明显差异(均P> 0. 05)。CO组在6 h、12 h、24 h各时间点的p-p38 MAPK表达量与BC组比较,差异均有统计学意义(均P <0. 05),其在24 h时间点的p-p38 MAPK的表达量最多,达峰值。CO组大鼠在造模后6 h、12 h、24 h各个观察时间点的皮质区AQP1光密度值均高于BC组(均P <0. 05)。结论大鼠急性CO中毒后脑皮质AQP1蛋白表达的上调,可能参与了CO中毒后脑水肿的病理生理过程。CO中毒后,大鼠脑皮质AQP1表达的变化伴随GFAP、p-p38 MAPK的改变,其机制可能是通过激活p-p38MAPK信号传导通路,上调AQP1、GFAP的表达,引起脑组织水肿。AQP1可能成为急性CO中毒脑损伤机制研究的新靶点。Objective To investigate the effect of aquaporin 1 (AQP1)expression and the potential mechanism on brain tissue damage in rat after acute carbon monoxide (CO)poisoning. Methods A total number of 112 male healthy SD rats were randomly assigned to the blank control group (BC group,n=8),the acute CO poisoning group (CO group,n=8). CO group was injected intraperitoneally with CO to establish the model,while BC group was injected with an equal volume of air. The frontal cortex tissues were collected at 3,6,12,24,48 and 72 h and 7 d after making the model. The levels of AQP1,AQP4,p38 MAPK,p-p38 MAPK and GFAP were measured by Western blotting analysis and immunohistochemistry staining. Results Western blotting showed,the level of AQP1 protein in the CO group was significant higher at 6,12 and 24 h than that of BC group (all P<0.05). The average AQP1 expression level of the CO group peaked in the cerebral frontal cortex at 24 h. The level of GFAP protein at 6、12 and 24 h in CO group was significant higher than that of the BC group(all P<0.05).The most quantity of GFAP in rat brain tissues was expressed at the 24 h after acute CO poisoning. The level of p38 MAPK protein was not statistically significant at 3,6,12,24,48 and 72 h and 7 d between the CO and BC groups (all P>0.05).The level of p-p38 MAPK protein at 6,12 and 24 h was obviously statistical significance in CO group(all P<0.05).The p-p38 MAPK levels had maximal expression at 24 h in CO group,reached the apex . The average optical density value of AQP1 protein was increased significantly at 6,12 and 24 h after CO poisoning than that of the BC group (all P<0.05). Conclusions The up-protein perhaps participate in the pathophysiological process of brain edema formation in rat regulation of AQP1 frontal cortex after acute CO poisoning. After CO poisoning,expression of AQP1 change go with variation of the GFAP and p-p38 MAPK proteins in rat frontal cortex. The mechanism of cerebral edema may be activated the signaling pathways of p-p38 MAPK that raise the expression

关 键 词：急性一氧化碳中毒 脑水肿 水通道蛋白1 GFAP P38 MAPK 

分 类 号：R595[医药卫生—内科学]