依达拉奉改善大鼠血脑屏障损伤的AQP-4机制研究

Research on acting mechanism of edavarone on AQP-4 in rats with blood brain barrier injury after acute cerebral hemorrhage

目的研究大鼠脑出血后血脑屏障（BBB）通透性与水通道蛋白4（aquaporin-4，AQP-4）的关系及依达拉奉的干预作用。方法采用自体动脉血注入尾状核法制成大鼠脑出血模型，免疫组化法观察AQP-4的表达，伊文思蓝法测BBB的通透性，干湿重法计算脑含水量表示脑水肿。结果与对照组相比，模型组及依达拉奉组BBB通透性均在出血后6h开始升高，1～3d最高，依达拉奉组明显小于模型组（P〈0．01）。2组AQP-4也于6h开始升高，1～3d达到高峰依达拉奉组明显小于模型组（P〈0．05）。BBB通透性与AQP-4表达呈显著正相关（r=0．880，P％0．01），与脑水肿变化趋势一致。结论脑出血后产生的AQP-4增多，从而增加BBB通透性，参与脑水肿形成和发展，依达拉奉可抑制AQP-4的表达，从而有减轻脑水肿的作用。

Objective To investigate the relationship between blood-brain spinal fluid barrier （BBB） permeability and aquaporin-4 （AQP-4）and the effect of edavarone after experimental intracerebral hemorrhage （ICH） in rats. Methods The ICH model were established by stereotaxie injection of autologous artery blood into caudate nucleus to detect AQP-4 expression by immunohistochemical method, BBB permeability by EB method and brain water contents by dry wet weight method. Results In contrast to the controlled group, BBB permeability increased at 6 hours in ICH group and edavarone group after ICH, reached peak at 1-3 days, and which in edavarone group was lower than that in ICH group （P〈0.05）. Edavarone expression increased at 6 hours in two groups reached peak at 3 days , and which in edavarone group was lower than that in ICH group （P 〈CO. 05）. There was a significantly positive correlation between AQP-4 expression and BBB permeability （r = 0. 880, P 〈 0.01）. Conclusion After ICH AQP-4 expression up regulate and BBB permeability increase, which could be inhibited by edav arone.