白藜芦醇对脑缺血大鼠海马β淀粉样蛋白和Tau蛋白的影响

Effects of resveratrol on amyloid-beta and Tau protein expression following cerebral ischemia in rats

目的:观察白藜芦醇对实验性脑缺血大鼠海马神经元β淀粉样蛋白(Aβ42)和磷酸化Tau蛋白(pTau)表达影响及与学习记忆功能障碍的关系。方法:选取Wistar雄性成年大鼠96只,按随机数字表法分为假手术组、脑缺血组、白藜芦醇组。采用线拴法建立左侧大脑中动脉脑缺血大鼠模型。采用Morris水迷宫测试各组大鼠学习记忆能力;干湿重法测定脑组织含水量;免疫组织化学法检测Aβ42和p-Tau在海马CA1区的分布情况;Western Blot法检测Aβ42、Tau,p-Tau在海马CA1区的蛋白表达量。结果:脑缺血组较假手术组相比脑组织含水量增加,逃避潜伏期延长,穿越平台次数及平台象限停留时间均减少,并且海马CA1区Aβ42和p-Tau蛋白的表达显著上调,差异均有统计学意义(P<0.05)。白藜芦醇可显著减少脑组织含水量,改善学习和记忆功能障碍,下调海马CA1区Aβ42和p-Tau蛋白的表达,差异均有统计学意义(P<0.05)。结论:白藜芦醇可改善脑缺血大鼠脑水肿及学习记忆障碍,这种脑保护作用可能与下调海马CA1区Aβ42和p-Tau蛋白的表达相关。

Objective： To explore the effect of resveratrol（Res） on amyloid-beta protein（Aβ42） and p-Tau protein expression,as well as it＇s relation to cognitive function in the rat model of cerebral ischemia. Methods： Ninety-six male adult Wistar rats were divided randomly into sham group,ischemia group（ model group） and Res group. Cerebral middle artery was occluded with nylon suture to establish middle cerebral artery occlusion model. Morris＇ water maze test was performed to evaluate learning and memory ability. The water content was calculated by dry and wet weight method. The cellular localization of Aβ42 and p-Tau protein in the neurons of hippocampal CA1 region was investigated by immunohistochemistry. The expression of Aβ42,Tau and p-Tau protein in the CA1 region of the hippocampus were detected by Western Blot. Results： Compared with sham group,the brain water content increased,escape latency was more extended,the times of crossing the platform and residence time in platform quadrant were significantly reduced,and the expression of Aβ42 and p-Tau were significantly increased in the hippocampal CA1 region（ P〈 0. 05）. Resveratrol treatment could significantly down-regulat Aβ 42 and p-Tau expression,and improv cerebral edema and learning and memory dysfunction after brain injury（ P〈 0. 05）. Conclusion： Resveratrol has a neuroprotective effect on cerebral ischemia,which is related to the down-regulation of expression of Aβ42 and p-Tau protein in the hippocampal CA1 region after cerebral ischemia.