AQP4在大鼠脑缺血再灌注损伤过程中作用机制

目的:探讨AQP4在大鼠脑缺血再灌注损伤过程中对脑损伤、脑水肿形成等的影响以及作用机制。方法:采用SD大鼠复制脑局限性缺血再灌注模型,应用免疫组织化学方法检测脑内AQP4蛋白,记录大鼠神经功能缺损程度、血脑屏障通透性、脑水肿程度的动态变化。结果:1.脑局限性缺血再灌注损伤后脑内AQP4蛋白水平迅速降低,至再灌注后12～24小时达最低水平,至再灌注7天时恢复到正常水平。2.脑水肿程度峰值出现在再灌注损伤第24～72小时、Evans蓝最大通透率出现在再灌注损伤第24～72小时。3.神经功能缺损最重的时间点出现在再灌注损伤的第24小时。4.分析再灌注24小时伤侧半球AQP4与同时间点的神经功能缺损评分的相关性,结果显示AQP4水平与神经功能缺损评分呈负相关性(R=-0.9767,P=0.023)。结论:1.脑缺血再灌注损伤过程中AQP4水平的迅速下降,是机体对脑损伤所作出的一种保护性反应,具有阻止血脑屏障破坏、减轻血管源性脑水肿和细胞源性脑水肿的效应。2.调节缺血后脑内AQP4的功能和表达水平可望成为新的治疗脑缺血再灌注损伤的靶点。

The change of AQP4 expression and its relation with cerebral injury following cerebral ischemia and reperfusion in rat

Objective;To invesigate the dynamic change of cerebral AQP4 expression level during ischemia, and reper-fusion. To examine hte relation between the relation between AQP4 expre-ssion and cerebral injury and adema. Methods; Cerebral ischemia and reperfusion model in SD rat (blood flow blocked for 2 hours and then reperfusion for 3hr,6hr, 12hr,24hr,72hr,7d). Irnmunohistochemistry staining and semi-quantitation analysis were performed to detect the cerebra AQP4. Life vital signs, permeability of BBB, neurological defictit scores, cerebral edema were recorded. Results: ① AQP4expression decreased quickly on the injured side of cerebrum, and it reached the lowest point at 12-24hr post-ischemia and re-perfusion. Then it increased slowly, and went back to normal till Day 7. ②The severest cerebral edemal was at 24-72hr post-reperfusion. while the highest permeability of the BBB was at 24-72hr post-repertusion. ③Neurlolgi-cal deficit score showed that the severest neurlolgical deficit was at 24hr post-reperfusion, the mortality of rats was highest at 24hr post -reperfusion. ④ The expression of AQP4 was examined on both sides of cerebrum 24hr post-ishcemic reperfusion. AQP 4 expression is negative co-related with neurological deficit score. Conclusion: 1). Decreased AQP4 expression post-ischemicre-perfusion was a protective response to BBB, because it could reduce vascular cerebral edema and cytotoxic cerebral edema. 2). The regulation of cerebral AQP4 expression post-ischemic reperfusion can be a new stategy for the treatment of post-ischemicreperfusion injury.