急性高原缺氧大鼠脑损伤及其水通道蛋白1／4的表达研究  

Research on brain damage and expressions of aquaporin 1/4 in rats exposed to acute high-altitude hypoxia

作　　者：李建宇[1] 祁玉婷[1] 郭鹏[1] 张永亮[2,3] 高宏生[3] 李灵芝[1,3] 

机构地区：[1]武警后勤学院药物化学教研室,天津300162 [2]武警后勤学院科研部,天津300162 [3]天津市职业与环境危害生物标志物重点实验室,天津300162

出　　处：《中国中西医结合急救杂志》2012年第6期326-329,共4页Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care

基　　金：国家自然科学基金项目（81073152）;天津市应用基础及前沿技术研究计划（10JCZDJC21100）;天津市重点实验室开放基金项目（WZK200901）;中国博士后科学基金（20100470106）

摘　　要：目的观察急性高原缺氧大鼠脑组织损伤及其水通道蛋白1，4（AQP1/4）的表达情况。方法将60只雌性SD大鼠按完全随机方法分为正常对照组及缺氧6、12、24h组，每组15只。利用数控低压舱建立急性高原缺氧模型。苏木素-伊红（HE）染色观察大鼠脑组织的损伤情况；用于湿差值法检测缺氧前后脑组织含水量的变化；采用酶学定量手段分析脑组织超氧化物歧化酶（SOD）活性及丙二醛（MDA）含量；应用蛋白质免疫印迹法（western blotting）检测脑组织AQP1/4的表达情况。结果各缺氧组大鼠出现了不同程度的脑组织损伤，表现为细胞胞体缩小，核固缩、溶解，且损伤程度随缺氧时间延长逐渐加重。与正常对照组比较，各缺氧组大鼠脑含水量显著升高，SOD活性（U／mg）显著降低，MDA含量（nmol／mg）明显增加（P〈0．05或P〈0．01），且与缺氧时间呈依赖性；脑组织中AQP1/4蛋白表达量均显著升高（均P〈0．01），且随缺氧时间延长变化更显著[24h脑含水量：（84．32±2．14）％比（70．44±1.83）％，SOD：95．541±6．651比137．743±4．890，MDA：1．271±0．302比0．592±0．055，AQP1：0．879±0．035比0．443±0．025，AQP4：0．854±0．031比0．577±0．048，均P〈0．019。结论急性高原缺氧可造成脑水肿等严重的脑组织损伤，其机制可能与上调AQP1，4的表达有关。Objective To explore the brain damage and expressions of aquaporin 1 and 4 （AQP1/4）in rats exposed to acute high-altitude hypoxia. Methods Sixty female Sprague-Dawley （SD） rats were divided into normal control group and hypoxia groups of 6, 12 and 24 hours on a completely random basis, each n = 15. The acute high- altitude hypoxic model was established by a designed decompression chamber. After exposure to hypoxia, the injuries of cerebral cortex were observed by hematoxylin-eosin （HE） staining, and water contents in brain were determined by the wet-dry method. The biochemical markers like superoxide dismutase （SOD） and malondialdehyde （MDA） in cerebral tissue were determined by enzymatic analysis, and the expressions of AQP1/4 in brain tissue were determined individually by Western blotting. Results The morphological changes of cerebral cortex in various hypoxia groups were observed, showing different degrees of cerebral injury, including cyton contraction, karyopyknosis, karyolysis and cytoplasm concentration. With the increase of hypoxic duration, the degree of brain damage became gradually more serious. Compared with normal control group, the water contents in cerebra were significantly enhanced in hypoxia groups, the activities of SOD （U/mg） were remarkably depressed, and the contents of MDA （nmol/mg） were increased （P〈0.05 or P〈0.01 ） in the brain of hypoxia groups, which were dependent on the length of hypoxia exposure ; the expressions of AQP1/4 in brain tissue were significantly increased after exposure to hypoxia （all P〈0.01 ）, and the up-regulation of AQP1/4 was more obviously enhanced with the increasing duration of hypoxia [ brain water contents ： （84.32±2.14） % vs. （70.44±1.83） %,SOD： 95.541±6.651 vs. 137.743±4.890, MDA： 1.271±0.302 vs. 0.592±0.055, AQPI ： 0.879±0.035 vs. 0.443±0.025, AQP4 ： 0.854±0.031 vs. 0.577±0.048, all P〈0.01]. Conclusion Acute high-altitude hypoxia causes severe damages of brain tissue, such as cerebral ed

关 键 词：高原缺氧 脑损伤 脑水肿 水通道蛋白1 4 

分 类 号：R651.1[医药卫生—外科学] R188[医药卫生—临床医学]