D-丝氨酸对精神分裂症模型大鼠学习记忆功能的影响

发布时间：2018-02-27 14:43

  本文关键词： 精神分裂症 D-丝氨酸 Morris水迷宫 学习记忆　出处：《皖南医学院》2017年硕士论文　论文类型：学位论文

【摘要】：目的:观察D-丝氨酸对MK-801诱导的精神分裂症模型大鼠学习记忆功能的影响,并对其相关的神经电生理机制进行初步探讨。方法:取60只青春期雄性SD大鼠随机均分为6组(n=10):正常对照组(C)、生理盐水组(NS)、MK-801模型组(MK)、MK-801模型给D-丝氨酸低剂量组(MK+D1)、MK-801模型给D-丝氨酸高剂量组(MK+D2)和MK-801模型给利培酮组(MK+RIS)。正常对照组无任何处理,生理盐水组大鼠腹腔注射生理盐水(1ml/kg,ip,qd)14 天,其余 4 组腹腔注射 MK-801(0.2mg/kg,ip,qd)造模 14 天,并对各组大鼠进行旷场试验、强迫游泳及Y迷宫等行为学试验。造模结束24h后,生理盐水组和MK-801模型组大鼠腹腔注射生理盐水(1ml/kg,ip,qd),其余三组分别给 D-丝氨酸(400mg/kg、800mg/kg,ip,qd)和利培酮(1mg/kg,ig,qd)10 天,再重复行为学试验,并利用Morris水迷宫进行学习记忆功能检测。之后对各组大鼠制备离体海马脑片,应用CA1区锥体神经元细胞内记录技术,记录并分析细胞电生理特性、兴奋性突触后电位(excitorypostsynapticpotential,EPSP)及其长时程增强(long-term potentiation,LTP)。结果:1.旷场实验结果分析药物干预前MK组、MK+RIS组、MK+D1组、MK+D2组4组大鼠的外周区活动路程、活动总路程、T1时间段活动路程、T2时间段活动路程及T3时间段活动路程均多于NS组和C组(P0.05或P0.01)。药物干预后,MK组的上述活动路程仍多于NS组、C组(P0.05或P0.01),而MK+RIS组、MK+D1组、MK+D2组3组均少于药物干预前(P0.05或P0.01)和MK组(P0.05或 P0.01)。2.强迫游泳实验结果分析药物干预前MK组、MK+RIS组、MK+D1组、MK+D2组4组大鼠的游泳不动时间均长于NS组和C组(P0.01)。药物干预后,MK组的游泳不动时间仍长于NS组、C组(P0.05);而MK+RIS组、MK+D1组、MK+D2组3组的游泳不动时间均短于药物干预前(P0.05)和MK组(P0.05或P0.01)。3.Y-迷宫实验结果分析药物干预前MK组、MK+RIS组、MK+D1组、MK+D2组4组大鼠的Y-迷宫交替百分率低于C组(P0.05)。药物干预后,MK组的交替百分率低于NS组、C组(P0.01);而MK+RIS组、MK+D1组、MK+D2组3组的交替百分率则高于药物干预前(P0.05或P0.01)和MK组(P0.01)。4.Morris水迷宫实验结果分析Morris水迷宫定位航行实验7天的逃避潜伏期分析显示,测试日间(P0.01)、处理组间(P0.05)差异均有统计学意义,两两比较表明,MK+D2组与MK组、MK+RIS组、MK+D1组及C组差异有统计学意义(P0.05或P0.01),且测试第3天处理组间(P0.05),MK+D2组与MK组和C组间(P0.01)差异均有统计学意义。测试第3天运动路程分析亦显示处理组间(P0.05),MK+D2组与MK组和C组间(P0.01)差异均有统计学意义。7天的游泳策略分析显示各组大鼠的分析策略构成比在第1、2、5、7天差异有统计学意义(P0.05或P0.01)。结论:对青春期大鼠腹腔注射MK-801可诱导精神分裂症模型,D-丝氨酸对其拟精神分裂症的阳性症状、阴性症状及认知功能缺陷均有改善效果,对其学习记忆功能可能存在一定影响。
[Abstract]:Objective: To observe the effect of D- serine split disease model of learning and memory function in rats with MK-801 induced by the spirit, and electrophysiological mechanism of the related was discussed. Methods: 60 male SD rats were randomly divided into 6 groups (n=10): normal control group (C), saline group (NS), MK-801 model group (MK), MK-801 model to D- serine low dose group (MK+D1), MK-801 model to D- serine in high dose group (MK+D2) and MK-801 (MK+RIS) model to risperidone group. Normal control group without any treatment, the saline group rats received intraperitoneal injection of saline (1ml/kg, IP, QD) 14 days, the remaining 4 groups received intraperitoneal injection of MK-801 (0.2mg/kg, IP, QD) 14 day of modeling, and open field test in rats, forced swimming and Y maze behavior test modeling. After the end of 24h, normal saline group and MK-801 group rats received intraperitoneal injection of saline (1ml/kg IP, QD), the rest. Three groups were given D- (400mg/kg, 800mg/kg, Ser IP, QD) and risperidone (1mg/kg, Ig, QD) for 10 days, then repeat the behavior experiment, and the learning and memory function detected by Morris water maze. After the rats were prepared from hippocampal slices using CA1 pyramidal neurons the intracellular recording techniques, analysis of cell electrophysiological properties and recorded excitatory postsynaptic potentials (excitorypostsynapticpotential, EPSP) and long-term potentiation (long-term, potentiation, LTP). Results: 1. the results of the open field of drug intervention before the MK group, MK+RIS group, MK+D1 group, MK+D2 group, the 4 groups of rats peripheral area of the total distance, T1 distance, time distance, T2 distance and time T3 time distance were more than that of NS group and C group (P0.05 or P0.01). After drug intervention, MK group of the distance is still higher than that of group NS, group C (P0.05 or P0.01), and MK+RIS group, MK+D1 group, M K+D2缁，

本文编号：1543103