脑室注射同型半胱氨酸对脑缺血大鼠β淀粉样蛋白及认知功能的影响  

Effects of intraventricular injected homocysteine on amyloid-beta protein expression and cognitive function in rats with cerebral ischemia

作　　者：张维文[1] 王晓莉[1] 孟伟建[1] 崔永健[1] 靳云姗[1] 卢蕾[1] 魏琰[1] Zhang Weiwen Wang Xiaoli Meng Weijian Cui Yongjian Jin Yunshan Lu Lei Wei Yan(Department of Neurology, Harrison International Peace Hospital, Hengshui 053000, Chin)

机构地区：[1]哈励逊国际和平医院神经内二科,衡水053000

出　　处：《解剖学杂志》2017年第1期26-30,共5页Chinese Journal of Anatomy

基　　金：河北省科技支撑计划项目(132777220)

摘　　要：目的:观察脑室注射同型半胱氨酸(Hcy)对实验性脑缺血大鼠脑组织β淀粉样蛋白(Aβ)的表达及学习记忆的影响。方法:Wistar雄性成年大鼠按随机数字表法分为假手术组、脑缺血组、Hcy组。采用线栓法建立左侧大脑中动脉脑缺血大鼠模型,2 h后同侧脑室立体定向注射Hcy(3μmol/L)。采用Morris水迷宫测试各组大鼠学习记忆能力;化学定量法检测血浆中Hcy含量;免疫荧光组织化学检测Aβ42、β-分泌酶(BACE1)在海马CA1区神经元中的共定位;免疫印迹检测Aβ42、BACE1在海马CA1区中的表达变化;结果:与假手术组相比,脑缺血组逃避潜伏期延长,穿越平台次数及平台象限停留时间均减少,并且Aβ42和BACE1表达明显上调,差异均有统计学意义。Hcy脑室注射后显著增加Aβ42和BACE1表达,明显加重脑损伤后的学习和记忆功能障碍。结论:Hcy可以导致脑缺血大鼠的学习记忆功能障碍,海马CA1区Aβ42和BACE1表达升高可能是其机制之一。Objective： To study effects of intraventricular injected homocysteine （Hcy） on amyloid-heta protein （Aβ） expression and cognitive function in the rat model of cerebral ischemia. Methods： Male adult Wistar rats were divided randomly into sham group, model group and Hey group. Cerebral middle artery was occluded with nylon suture to establish middle cerebral artery occlusion model. Rats in Hey group were treated by intraventricular injection of Hcy （3 μmol/L） 2 h after the operation. Morris＇ water maze test was used to evaluate learning and memory ability. The level of Hey in the plasma was tested by chemical quantitative analysis. The eoloealization of Aβ42 and β-site-APP cleavage enzyme （BACE1） protein in the neurons of hippocampal CA1 region was observed by immun of luorescence histochemistry. The expression of Aβ342 and BAGEl protein in the CA1 region of the hippocampus was detected by Western blotting. Results： Compared with sham group, escape latency was more extended, and the times of crossing the platform as well as residence time in platform quadrant were significantly reduced, and the expression of Aβ42 and BACE1 was significantly increased in the hippocampal CA1 region in the model group. Hey could significantly further upregulate Aβ42 and BACE1 expression, and promote learning and memory dysfunction after brain injury. Conclusion： Learning and memory dysfunction after cerebral isehemia can be induced by Hey treatment, which may be associated with the upregulated expression of Aβ42 and BACE1 protein in the hippocampal CA1 region after cerebral ischemia.

关 键 词：同型半胱氨酸 脑缺血 Β淀粉样蛋白 Β分泌酶 学习记忆 大鼠 

分 类 号：R741[医药卫生—神经病学与精神病学]