水通道蛋白4在大鼠轻度脑外伤后脑水肿形成中的作用

Role of aquaporin-4 in the formation of brain edema after mild traumatic brain injury in rat

目的:通过研究大鼠脑外伤后,血脑屏障(BBB)通透性的改变和水通道蛋白4(AQP4)的表达变化,探讨其在脑外伤后脑水肿的形成、发展及转归中的作用,为临床治疗脑水肿提供依据。方法:采用伊文蓝测定法、免疫荧光双标显色、RT-PCR、干湿重法,分别检测BBB损伤程度,AQP4的表达,双侧大脑皮质、海马AQP4mRNA的含量变化和脑含水量。结果:伤侧大脑BBB损伤于脑外伤后1～24h明显,以1h为甚,之后逐渐减轻;对侧则于伤后6～48h损伤明显。免疫荧光双标和RT-PCR结果基本一致,双侧皮质AQP4及其mRNA于3h增高,随后先降低再升高,至48～72h达峰值;双侧海马几乎于各时段均呈显著降低。双侧皮质、海马含水量均于6h显著增加,并达峰值,之后先略有下降后再次增加,至48～72h达次高峰。结论:脑外伤早期,AQP参与了细胞外水肿的清除,其表达的下调和BBB的损伤,导致细胞外水肿形成。脑外伤继发损伤期,AQP4参与了细胞外水肿的清除和细胞内水肿的形成。

Objective： To explore the role of altered aquaporin-4 （AQP4） expression and blood brain barrier （BBB） integrity in formation and development of brain edema in the cortex and hippocampus after mild traumatic brain injury （TBI） in rats. Methods： Evan blue, immunofluoreseence, RTPCR and dry-wet weight method were used respectively to measure the in- tegrity of BBB, the expression of AQP4, the expression of AQP4 mRNA and the extent of brain edema. Results： BBB was markedly impaired in the period of 1-24 h with gradual attenuation in injured hemicerebrum and at 6-48 h in opposite side after TBI. The expression of AQP4 and its mRNA was increased at 3 h and deereased at 6 h, and then increased again and reached the peak at 48 72 h in the cortex after TBI. However, in hippocampus, they were decreased almost in the whole stage after TBL The water content of the cortex and hippocampus was greatly increased and reached the peak at 6 h after TBI. Following a little decrease, it was increased again and reached the second peak at 48-72 h after TBI. Conclusion： The decreased AQP4 impedes the elimination of edema fluid in extracellular space, and the impaired BBB induces extracellular brain edema in earlier stage after TBI. Although the increased AQP4 was involved in elimination of brain edema, it still induced cellular brain edema in later stage after TBI.