脑出血后水通道蛋白4与内向整流性钾通道4．1的再分布与脑水肿形成的关系

Relationship between redistribution of aquaporin 4 and Kir4. 1 and brain edema after intracerebral hemorrhage

目的：探讨水通道蛋白4（AQP4）与内向整流性钾通道4．1（Kir4．1）在出血性脑水肿形成中的作用。方法：采用胶原酶注入法建立脑出血（ICH）模型，运用干湿重法、伊文氏蓝（EB）测定法、荧光双标和RT-PCR分别检测ICH后脑水含量（BWC）、血脑屏障（BBB）通透性、AQP4与Kir4．1及两者mRNA的表达变化，并对每一时间点AQP4mRNA、Kir4．1mR—NA表达量做比值分析。结果：ICH后3hBWC已明显增高，至48h达到峰值；EB含量在KH后48h内高于对照组，以6h最甚；荧光双标显示，AQP4与Kir4．1强弱不等地表达在双侧软脑膜、室管膜、脉络膜等与水代谢密切相关的界面上。ICH后6h及其以后时段，两者的mRNA均明显增高，且于48h达到峰值；比值分析显示，ICH后6h及以后时段，AQP4mRNA的增加量明显大于Kir4．1mRNA的增加量。结论：ICH早期的脑水肿主要由血脑屏障通透性增加所致，而ICH中后期的脑水肿主要由AQP4与Kir4．1的再分布引起。

Objective： To explore the roles of aquaporin 4 （AQP4） and Kir4. 1 in the brain edema after intracerebral hemorrhage （ICH）. Methods： Collagenase was infused into the caudate nucleus to establish an ICH model. The changes of brain water content （BWC） were measured by wet and dry weight methods. Evan＇s blue （EB） was used to measure the integrity of blood brain barrier. The expressions of AQP4 and Kir4. 1 were detected by immunofluorescence, and the contents of AQP4 mRNA and Kir4.1 mRNA were detected by RT-PCR. The ratio analysis of AQP4 mRNA and Kir4.1 mRNA was performed. Results： BWC was increased at 3 h after ICH and reached its peak at 48 h. Among 48 h after ICH, EB contents were increased, and reached its peak at 6 h. AQP4 and Kir4. 1 were co-expressed at cerebral pia mater, choroid plexus and ependyrna. The contents of AQP4 mRNA and Kit4. 1 mRNA were increased at 6 h after ICH, and reached their peaks at 48 h. The ratios of AQP4 mRNA and Kir4. 1 mRNA were increased at 6 h after ICH. Conclusion： In the early stage after ICH, the increased capillary vessel permeability may induce the brain edema, and in the later stage, the redistribution of AQP4 and Kir4. 1 plays an important role in the pathological course of the hemorrhagic cerebral edema.