The Study Of Mannitol's Effect On Aquaporin-4 Expression Of Ischemic Cerebral Edema

[Objective]To study the aquaporin-4(AQP4) expression and the effect of mannitol on aquaporin-4 after cerebral ischemia; to observe the changes of the brain water content , permeability of blood-brain barrier and the influence of mannitol after cerebral ischemia.[Methods]1. Weighing 250~300g SPF male SD rats, the middle cerebral artery thrombosis models were established by using suture method, 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). In each groups, 5 rats were randomly selected and decapitated at the time points of 6h, 12h, 1d and 3d after cerebral ischemia; meanwhile, we also establish sham group (n=5).2. 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) was used to detect the expression of AQP4.[Results]1. In low dose group, high dose group and control group, brain water content in ischemic tissues increased after cerebral ischemia, and reached 3d as the highest point (P<0.05), no significant difference was observed among 3 groups(P>0.05); no significant difference was observed among each time points in the contralateral corresponding position(P>0.05), and no significant difference was observed among 3 groups(P>0.05).2. In low dose group, high dose group and control group, the Evans blue in ischemic tissues increased after cerebral ischemia, and reached 1d as the highest point (P<0.05), no significant difference among 3 groups(P>0.05); the Evans blue in the contralateral corresponding position reached 1d as the highest point (P<0.05), no significant difference among 3 groups(P>0.05). 3. In control group, the expression of AQP4 mRNA in peri-ischemic cortex reached 1d as the highest point, then declined at 3d, but still at high level(P<0.05); and data obtained in the low dose group and high dose group were significantly lower than control groups (P<0.05), and there was no significant difference between low dose group and high dose group(P>0.05); no significant differences was observed among each time points in the contralateral corresponding position(P>0.05), and no significant differences was observed among 3 groups(P>0.05).[Conclusion]1. The dynamic changes of expression of AQP-4mRNA in rat peri-ischemic cortex after cerebral ischemia suggest that AQP4 is closely related to the occurrence and development of cerebral edema;2. Mannitol can significantly reduce the expression of AQP4mRNA in peri-ischemic cortex, which suggests that mannitol is a disincentive for AQP4.3. The role of AQP4 is a result which in response to the changes of osmotic pressure, thus we can not effectively explain the pathophysiology of cerebral edema and anti-edema drugs by only adopting AQP4 as the single factor for study, instead we should integrate AQP4 with another ion channels in the cell membrane as a whole for study.