脑缺血再灌注大鼠脑组织水孔蛋白4的动态表达及其与脑水肿的关系

目的 探讨水孔蛋白4（aquaporin-4，AQP-4）在大鼠脑缺血再灌注后的动态表达及其与脑水肿的关系。方法 60只健康成年雄性SD大鼠，随机分成2组：大脑中动脉闭塞/再灌注（middle cerebral artery occlusion/reperfusion，MCAO/R）组和假手术组，采用Longa、Berderson、平衡木评分法进行行为学评分，干-湿重法测定脑组织含水量，HE染色观察大鼠脑组织的病理改变，免疫组化法检测脑组织AQP-4的表达。结果 MCAO/R组大鼠行为学异常，以48 h和72 h为著，7 d时已基本恢复至正常水平；脑含水量24 h开始升高（82.42%±0.12%），48 h达高峰（85.40%±0.10%），并持续到72 h（84.87%±0.15%），7 d时下降至大致正常水平。脑水肿及炎性细胞浸润，以48 h和72 h为著。AQP-4阳性表达于梗死后6 h开始增多（110.0±4.4），48 h～72 h达高峰（126.2±2.6；140.1±1.2），7 d时有所下降（111.3±8.0），但仍处于较高水平，与假手术组比较，差异有统计学意义（P<0.05）。结论 脑缺血再灌注后脑组织AQP-4的表达的变化与脑水肿的动态变化存在时间上的一致性，提示AQP-4可能参与了早期脑缺血再灌注后脑水肿形成的病理生理过程，而后期可能与脑内多余水分的清除有关。

The Dynamic Expression of AQP-4 in Cerebral Ischemic-Reperfussion Model in Rats and the Correlation with Brain Edema

Objective To investigate the Aquaporin-4(AQP-4) expression after cerebral ischemic-reperfussion of rats and the relationship between AQP-4 expression and brain edema.Methods Total 60 adult male Sprague-Dawley rats were randomly divided into sham operation group and middle cerebral artery occlusion/reperfussion(MCAO/R) group. All the rats were tested for neurological behavior by using three different methods: Longa, Berderson and balance beam tests. Brain water content was measured by the wet-dry method and we observed the pathology changes by hematoxylin and eosin(HE) dyeing,the expression of AQP-4 by immunohistochemistry staining.Results In MCAO/R group: the behavioral outcomes were most serious at 48 h and 72 h , back to normal at 7 d; the brain water content increased at 24 h(82.42±0.12)%], reached to maximum at 48 h (85.40±0.10)%]and continued to 72 h (84.87±0.15)%],decreased to normal at 7 d; conspicuous edema and inflammatory cell infiltrating observed by HE dyeing, were most obviously at 48 h and 72 h but disappeared at 7 d; the expression of AQP-4 gradually increased at 6 h (110.0±4.4), reached its peak at 48 h - 72 h (126.2±2.6; 140.1±1.2), and reduced at 7 d (111.3±8.0), but also higher than sham operation group significantly, P<0.05.Conclusion The phase consistency is obvious between the change of expression of AQP-4 and dynamic state process of brain edema, which suggest AQP-4 probable take effect in pathophysiological course of brain edema in the early phase of phase of cerebral ischemic-reperfusion. And inthe late phase AQP-4 may play an important role in the clearance of redundant brain water.