亚低温治疗对脑缺血大鼠AQP4基因表达及血脑屏障通透性的影响

Influence of mild hypothermia on the expression of AQP4 and the permeability of blood-brain barrier after rat cerebral ischemia

目的观察亚低温治疗对脑缺血大鼠AQP4表达和血脑屏障通透性的变化的影响,探讨亚低温减轻缺血性脑水肿的可能机制。方法线栓法制作脑缺血大鼠模型,实验分常温组、亚低温组和假手术组,分别在缺血后6h、24h、48h、72h用干湿重法测脑组织含水量,荧光法检测血脑屏障通透性的改变,原位杂交检测AQP4的表达变化。结果假手术组脑组织含水量、血脑屏障通透性、AQP4表达无变化。缺血组脑组织含水量和血脑屏障通透性增加,AQP4表达上调,缺血48~72h变化最显著。相同时间点常温组脑组织含水量和血脑屏障通透性增加、AQP4的表达上调比亚低温组明显,两组之间的差异具有统计学意义（P〈0.05）。结论亚低温条件下AQP4表达下调、血脑屏障通透性和脑水肿程度减轻。亚低温可能通过下调AQP4表达、减轻血脑屏障通透性,减轻缺血性脑水肿。

Objective To study the influence of mild hypothermia on the expression of AQP4 and the permeability of blood-brain barrier（BBB）after rat cerebral ischemia,and to detect the mechanisms of mild hypothermia that decreases the water content in ischemic brain tissue.Methods Cerebral ischemic models were established by occluding unilateral middle cerebral arteries of rats with threads.The rats were divided into normal temperature（NT）group,mild hypothermic（MHT）group and sham operation group.The brain water content was measured by the wet-dry weighing method at the same times.The permeability of BBB was observed with fluorophotometry method and the expression of AQP4 was measured with in situ hybridization method on 6h,24h,48h and 72h after cerebral ischemia.Results In sham operation group,the brain water content,the permeability of BBB and the expression of AQP4 had no changes.The expression of AQP4 was up-regulated.The brain water content and the permeability of BBB in ischemic tissue increased.The changes became most obvious during 48h to 72h after cerebral ischemia.And the changes in NT were more serious than those in MHT group at the same time（P0.05）.Conclusions Under mild hypothermia,the expression of AQP4 was down-regulated,and the permeability of BBB and the brain edema decreased after cerebral ischemia.One of the mechanisms of mild hypothermia could decrease the water content in ischemic brain tissue,may be through down-regulation the expression of AQP4 and decreasing the permeability of BBB.