依达拉奉与甘露醇联合应用对大鼠脑梗死后脑组织内水通道蛋白-4表达的影响

Effect of Edaravone Combined with Mannitol on Expression of AQP4 mRNA After ischemic Brain Edema in Rats

【目的】探讨依达拉奉与甘露醇联合应用对大鼠脑梗死后脑组织内水通道蛋白-4（AQP-4）表达的影响。【方法】成年雄性Wistar大鼠150只，随机分为正常组、假手术组、手术未治疗组、甘露醇组、依达拉奉组、甘露醇与依达拉奉合用组（联合组）。采用Longa改良法制作大鼠脑梗死模型，各组分别于术后6h、d1、d2、d3、d7取损伤区脑组织，观察缺血脑组织形态变化及检测AQP-4 mRNA的表达并比较。【结果】正常组与假手术组脑组织无明显水肿，未治疗组大鼠缺血区的脑组织细胞及血管周围间隙扩大，部分细胞坏死，脑水肿于d3最明显，d7基本消退，甘露醇组未见脑水肿缓解、残留少许神经细胞；依达拉奉组和联合组脑组织水肿减轻、有较多的神经细胞保留。假手术组、依达拉奉组、联合组d1、d7组织中AQP-4 mRNA表达水平与对照组比较无显著性差异（P〉0．05），而假手术组6h、d2、d3均显著高于对照组（P〈0．05），依达拉奉组、联合组6h高于对照组（P〈0．05），d2、d3显著低于对照组（P〈0．05），依达拉奉组、联合组各时间点AQP-4mRNA表达水平比较均无显著性差异（P〉0．05）；未治疗组、甘露醇组随时间AQP-4 mRNA表达逐渐增多，d3达到高峰，之后下降，但在d7时还均高于对照组（P〈0．05）。【结论】AQP-4／TIRNA与脑水肿的过程密切相关，脑梗死后AQP-4mRNA的表达增加，依达拉奉联合甘露醇治疗能够下调AQP-4 mRNA的表达，缓解脑梗死后的脑水肿。

[Objective]The aim of this study was to investigate the change of aquaporin-4 （AQP-4）after treatment edaravone and mannitol in ischemic brain edema rats.[Methods]150 adult male Wistar rats were randomly divided into randomized to six groups ： normal, false surgery, surgery, mannitol（M ）, edaravone（E）, and edaravone combined with mannitol（E with M）.Modified Longa rat brain infarction model （middle cerebral artery occlusion） were applied. The morphological changes of ischemic brain and AQP4 mRNA expression were detected after surgery of middle cerebral artery occlusion and measured treatment at 6h, 1d, 3d, 5d and 7d after each treatment. [Results]Within the ischemic brain, the intercellular space and perivascular space became larger, some neurons showed necrosis phenotype, and the edema was most obvious at 3d and was relieved at 7d. After the treatment with mannitol, the edema was not alleviated and few neurons were seen. In the groups of E and E with M, the cerebral edema was alleviated and more neurons were found seen. After the cerebral infarction, the expression of AQP-4 mRNA increased, peaked at 3d, then decreased and returned to almost normal almostly at 7d（ P 〈0.05）. AQP-4 mRNA of group M was expressed less at the beginning first time, but then increased rapidly（ P 〈0.05） . The expression of AQP-4 in the group E and E with M remained low P 〈0.05）.[Conclusion]AQP-4 plays an important role in the formation of ischemic cerebral edema. The expression of AQP-4 mRNA increased after the cerebral infarction increased. Through the treatment of edaravone combined with mannitol, the expression of AQP-4 mRNA decreased and the brain edema was alleviated.