Abstract: Objective To study the aquaporin-4(AQP-4) expression after cerebral ischemia and the effect of mannitol on AQP-4.Methods The middle cerebral artery thrombosis model were established , randomly divided into three groups, low dose mannitol group (0.5g/kg, n=32), high dose mannitol group(1.0g/kg,n=32)and control group (n=32), and 5 rats were randomly decapitated at the time points of 6h, 12h,1d and 3d after cerebral ischemia (n=5 in each group). Meanwhile, we also establish sham group(n=5). Brain tissues were taken, the brain water content and permeability of Blood-brain Barrier were detected (Evans blue as a tracer), reverse transcription-polyrnerase chain reaction (RT-PCR) were used to detect the expression of AQP-4.Results In low dose group, high dose group and control group, brain water content in ischemic tissues increases after cerebral ischemia, and reaches 3d as the highest point (P <0.05), no significant differences is observed among groups(P >0.05); In low dose group , high dose group and control group, the Evans Blue in ischemic tissues increases after cerebral ischemia, and reaches 1d as the highest point (P <0.05), no significant differences between groups(P >0.05); In control group, the expression of AQP-4 mRNA in peri-ischemic cortex reaches 1d as the highest point, then declines at 3d, but still at high level(P <0.05); and there is a significant difference with low dose groupand high dose group (P <0.05), no significant differences between low dose group and high dose group(P >0.05).Conclusion The dynamic change regulation of expression of AQP-4 mRNA in rat peri-ischemic cortex after cerebral ischemia suggest that AQP-4 is closely related to the occurrence and development of cerebral edema; mannitol can significantly reduces the expression of AQP-4 mRNA in peri-ischemic cortex, and that mannitol is a disincentive for AQP-4.

Key words: Brain edema; Aquaporin-4; Mannitol

摘要： 目的 研究大鼠脑缺血后水通道蛋白4（aquaporin-4，AQP-4）的表达水平及甘露醇对其影响。方法 构建大脑中动脉闭塞模型，随机分为甘露醇治疗小剂量组（0.5g/kg）（n=32）、大剂量组（1.0g/kg）（n=32）和对照组（n=32），于梗死后6h、12h、1d、3d 各时间点随机抽取5只大鼠处死；另设假手术组5只。取脑组织分别作含水量、血脑屏障通透性测定（以伊文思蓝为示踪剂）及采用逆转录-聚合酶链反应（reverse transcription-polyrnerase chain reaction，RT-PCR）分析AQP4信使核糖核酸（Messenger ribonucleic acid，mRNA）的表达水平。结果 小剂量组、大剂量组及对照组缺血侧脑组织含水量在梗死后上升，3d到达高峰（P <0.05），各组间差异无统计学意义（P >0.05）；小剂量组、大剂量组及对照组缺血侧脑组织伊文思蓝含量在梗死后上升，1d到达高峰（P <0.05），各组间差异无统计学意义（P >0.05）；对照组缺血侧梗死灶周围皮质AQP－4 mRNA表达水平在梗死后1d到达高峰，3d开始回降，但仍处高水平（P <0.05），小剂量组、大剂量组与对照组相比显著降低（P <0.05），小剂量组与大剂量组相比差异无统计学意义（P >0.05）。结论 大鼠缺血性卒中后缺血侧梗死灶周围皮质AQP－4 mRNA表达水平动态变化规律提示，AQP4与脑水肿的发生发展密切相关；甘露醇可明显降低缺血侧梗死灶周围皮质AQP-4 mRNA表达水平，提示甘露醇对AQP-4有抑制作用。

关键词: 脑水肿; 水通道蛋白质4; 甘露醇