赵娟　张彦妹　郑乃智

[摘要] 目的 研究β-淀粉樣蛋白（Aβ）对癫痫（EP）发病机制的影响。 方法 按随机数字表法将40只6～8周Wistar大鼠分为Aβ1-42+PILO组、Aβ1-42组、PBS+PILO组、PBS组，每组各10只；前两组合称为Aβ1-42模型组，后两组合称为PBS对照组。采用脑立体定位仪在Aβ1-42模型组大鼠海马CA3区注入Aβ1-42，PBS对照组给予相同剂量的PBS。2周后观察大鼠Morris水迷宫实验，记录逃避潜伏期、目标象限内游泳时间比例和穿越平台次数，检测大鼠AD模型是否成功。建模成功后通过腹腔（IP）注射氯化锂-匹罗卡品（LI-PILO）制备大鼠慢性EP模型，依据Racine分级标准，记录EP发作潜伏期、发作程度和死亡率。 结果 Aβ1-42模型组和PBS对照组各有1只大鼠死亡。Morris水迷宫实验数据分析结果，Aβ1-42 模型组与PBS对照组大鼠相比，逃避潜伏期显著延长（P < 0.01），目标象限内游泳时间比例缩短（P < 0.05），穿越平台次数显著减少（P < 0.05），表明AD模型制备成功。制备大鼠EP模型：依据Racine分级标准，Aβ1-42+PILO组与PBS+PILO组相比，EP发作潜伏期显著缩短（P < 0.01），发作程度更重（P < 0.05）；Aβ1-42+PILO组与PBS+PILO组相比死亡率显著增加（P < 0.05）。 结论 通过海马CA3区注射Aβ1-42，可以导致大鼠出现与海马有关的学习和记忆功能受损。在Aβ存在的基础上诱导大鼠出现EP发作的易感性增加。

[关键词] β-淀粉样蛋白；癫痫；阿尔茨海默病；易感性

[中图分类号] R73 [文献标识码] A [文章编号] 1673-7210（2017）09（c）-0025-05

[Abstract] Objective To study the effects of β-amyloid protein （Aβ） on the pathogenesis of epilepsy （EP）. Methods 40 male Wistar rats were divided into Aβ1-42 + PILO group， Aβ1-42 group， PBS + PILO group and PBS group by random number table， with 10 rats in each group. The former two groups were called Aβ1-42 model group and the later PBS control group. Aβ1-42 and same volume PBS were injected into the hippocampal CA3 region of Wistar rats in Aβ1-42 model group and PBS control group by stereotaxic apparatus respectively， and the Morris water maze test was observed after 2 weeks. Escape latency， the percentage of swimming time in the target quadrant and the number of times of crossing the platform were recorded. After the AD model was successfully made， the rat model of chronic EP was established by intraperitoneal injection of LI-PILO. The latency of EP， degree of seizure and mortality of rats were recorded according to Racine grading criteria. Results One rat died in Aβ1-42 model group and the PBS control group. The results of Morris water maze test showed that compared with the PBS control group， the escape latency of the Aβ1-42 model group was longer （P < 0.01）， the proportion of swimming time in the target quadrant was shorter （P < 0.05）， and the number of crossing the platform was also significantly reduced （P < 0.05）. It indicated that the AD model was successfully prepared. Preparation of rats EP model： The latency of EP in Aβ1-42 + PILO group was significantly shorter （P < 0.01）， and the degree of seizure was more severe （P < 0.05）， compared with PBS + PILO group， according to Racine grading criteria. The mortality of rats in Aβ1-42 + PILO group was significantly increased compared with PBS + PILO group （P < 0.05）. Conclusion It can lead to the impaired hippocampus-related learning and memory function by injection of Aβ1-42 in hippocampal CA3 region of rats. The existing of Aβ increasing the susceptibility to EP in the rats， which indicates that Aβ plays a facilitation role in the occurrence of EP.endprint

[Key words] Beta amyloid protein； Epilepsy； Alzheimer disease； Susceptibility

癫痫（EP）是神经科常见疾病，长期EP发作导致近40%的患者出现认知功能障碍，且EP患者意外死亡的风险比普通人群高2～3倍[1-2]。近40年来老年患者占EP患者比例越来越高，继卒中后癫痫（PSE）发病率升高之外，EP和阿尔茨海默病（AD）之间的共病现象也得到越来越多的重视[3]。EP和AD之间相关性研究成为神经科学领域讨论的热点问题。本研究目的主要是通过动物实验，在行为学方面，研究β-淀粉样蛋白（Aβ）导致EP发作易感性增加及其机制。

1 材料与方法

1.1 动物选择及分组

选择SPF级雄性Wistar大鼠40只（动物合格证号：SCXK（鲁）20140007），周龄为6～8周，体重为200～220 g，每笼3～4只；室温保持（24±2）℃，室内湿度维持55%左右，12 h昼/夜循环灯光环境中，可自行获取固体食物和水，观察无自主EP发作入选。……