摘要
目的 探讨慢性脑缺血性认知功能障碍中蛋白磷酸酶2（Protein Phosphatase 2A,PP2A）的作用和潜在机制.方法 70只雄性清洁级Sprague Dawley （SD）大鼠,分为假手术组（sham）、慢性脑缺血组（Bilateral carotid arteries occlusion,2VO）和激活PP2A（active PP2A,aPP2A）慢性脑缺血组（2VO＋aPP2A）,持续4周腹腔注射1.88μmol/ml硒酸钠（15 μmol·kg^-1·d^-1）激活PP2A或等体积生理盐水作为对照,1个月后采用双侧结扎颈总动脉方法建立慢性脑缺血模型.利用Morris水迷宫、电生理和电镜技术,检测大鼠学习记忆能力,记录长时程电位变化,观察突触前膜突触囊泡分布.结果 Morris水迷宫测试显示在训练第4～7天2VO组大鼠较假手术组大鼠有明显长的平台学习潜伏期（P＜0.05）,而2VO＋aPP2A组则明显短于2VO组（P＜0.01）.去掉平台测试记忆显示,2VO组大鼠到达原平台位置时间明显长于假手术组[sham 组：（14.50±1.98）s vs 2VO组：（17.30±2.11）s,P＜0.01],而2VO＋aPP2A组所用时间[（15.09±1.45）s]则明显短于2VO组（P＜0.05）.电生理记录显示在高频刺激后2VO组的刺激前后兴奋性场电位斜率比即长时程增强（long-term potential,LTP）明显小于假手术组[假手术组：（1.69±0.27）;2VO组：（2.02±0.14）]（P＜0.01）,而2VO＋aPP2A组（1.86±0.19）则高于2VO组（P＜0.01）.电镜观察并分析后显示2VO组突触前膜突触囊泡的密度明显低于假手术组[假手术组：（4.51±0.29）个/μm^2;2VO组：（2.58±0.23）个/μm^2] （P＜0.01）,而2VO＋aPP2A组[（3.58±0.50）个/μm^2]则高于2VO组（P＜0.01）.结论 激活PP2A可能通过调节LTP和突触囊泡密度来预防慢性脑缺血性认知功能障碍,PP2A可能是一个潜在的慢性脑缺血性认知功能障碍的防治靶点.
Objective To explore the roles and related mechanisms of Protein Phosphatase 2A（PP2A） in cognitive dysfunction after the chronic cerebral ischemia.Methods 70 male Sprague Dawley rats in clean degree were divided into sham group,chronic cerebral ischemia group （Bilateral carotid arteries occlusion,2VO）,and chronic cerebral ischemia group with PP2A activation group（2VO＋aPP2A）.The rats were injected intraperitoneally with 1.88 μmol/ml sodium selenate（15 μmol · kg^-1 · d^-1） or equal volume of saline for 4 weeks.After one month,the chronic cerebral ischemia models were reproduced by the occlusion of bilateral common caroid artery.Then the abilities of learning and memory were tested by Morris water maze,electrophysiological indices were recorded to analyze the LTP changes,and destribution of synaptic vesicles was observed by electron microscope.Results Morris water maze test showed that the 2VO group had significantly longer latent time than sham group in searching platform（P〈0.05）,and the 2VO＋aPP2A group had dramatically shorter latent time （P〈0.01） than that of 2VO group.Then removing platform to test the rats memory,the data showed that 2VO group spent markedly longer time than sham group to reach the location of the former platform （sham group：（14.50±1.98）s ; 2VO group：（17.30±2.11） s） （P〈0.01）,and the 2VO＋aPP2A group（（15.09± 1.45） s） spent dramatically shorter latent time（P〈0.05） than that of 2VO group.The electrophysiological data showed that 2VO group had the noticeably smaller field excitable postsynaptic potential slope （fEPSP） slope ratio between pre and post of the high frequency stimulations （Long-term potential,LTP） than sham group（sham group：1.69±0.27; 2VO group：2.02±0.137） （P〈0.01）,and the 2VO＋aPP2A group（1.86±0.19） had strikingly higher ratio than that of 2VO group（P〈0.01）.The electromicroscope observation showed that presynaptic vesicles density of 2VO was remarkably lower than that of sham group （sham group：（4.51±0.29） /μm^2 ; 2VO group：（2.02±0.14） /μm^2） （P〈0.01）,and presynaptic vesicles density of 2VO＋aPP2A group（（3.58±0.50） /μm^2） was noticeably higher than that of 2VO group（P〈0.01）.Conclusion Activating PP2A can prevent the cognitive dysfunction after chronic cerebral ischemia through regulating LTP and synaptic vesicle density.And PP2A is probably a potential target for preventing and treating the cognitive dysfunction after chronic cerebral ischemia.
出处
《中华行为医学与脑科学杂志》
CAS
CSCD
北大核心
2014年第12期1075-1078,共4页
Chinese Journal of Behavioral Medicine and Brain Science
基金
武汉大学中央高校自主科研基金（2042014kf0116）
关键词
慢性脑缺血
蛋白磷酸酶2
学习和记忆障碍
Chronic cerebral ischemia
PP2A
Dysfunction of learning and memory
