本文關(guān)鍵詞： 精神分裂癥 D-絲氨酸 Morris水迷宮 學(xué)習(xí)記憶　出處：《皖南醫(yī)學(xué)院》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：目的:觀察D-絲氨酸對MK-801誘導(dǎo)的精神分裂癥模型大鼠學(xué)習(xí)記憶功能的影響,并對其相關(guān)的神經(jīng)電生理機制進行初步探討。方法:取60只青春期雄性SD大鼠隨機均分為6組(n=10):正常對照組(C)、生理鹽水組(NS)、MK-801模型組(MK)、MK-801模型給D-絲氨酸低劑量組(MK+D1)、MK-801模型給D-絲氨酸高劑量組(MK+D2)和MK-801模型給利培酮組(MK+RIS)。正常對照組無任何處理,生理鹽水組大鼠腹腔注射生理鹽水(1ml/kg,ip,qd)14 天,其余 4 組腹腔注射 MK-801(0.2mg/kg,ip,qd)造模 14 天,并對各組大鼠進行曠場試驗、強迫游泳及Y迷宮等行為學(xué)試驗。造模結(jié)束24h后,生理鹽水組和MK-801模型組大鼠腹腔注射生理鹽水(1ml/kg,ip,qd),其余三組分別給 D-絲氨酸(400mg/kg、800mg/kg,ip,qd)和利培酮(1mg/kg,ig,qd)10 天,再重復(fù)行為學(xué)試驗,并利用Morris水迷宮進行學(xué)習(xí)記憶功能檢測。之后對各組大鼠制備離體海馬腦片,應(yīng)用CA1區(qū)錐體神經(jīng)元細胞內(nèi)記錄技術(shù),記錄并分析細胞電生理特性、興奮性突觸后電位(excitorypostsynapticpotential,EPSP)及其長時程增強(long-term potentiation,LTP)。結(jié)果:1.曠場實驗結(jié)果分析藥物干預(yù)前MK組、MK+RIS組、MK+D1組、MK+D2組4組大鼠的外周區(qū)活動路程、活動總路程、T1時間段活動路程、T2時間段活動路程及T3時間段活動路程均多于NS組和C組(P0.05或P0.01)。藥物干預(yù)后,MK組的上述活動路程仍多于NS組、C組(P0.05或P0.01),而MK+RIS組、MK+D1組、MK+D2組3組均少于藥物干預(yù)前(P0.05或P0.01)和MK組(P0.05或 P0.01)。2.強迫游泳實驗結(jié)果分析藥物干預(yù)前MK組、MK+RIS組、MK+D1組、MK+D2組4組大鼠的游泳不動時間均長于NS組和C組(P0.01)。藥物干預(yù)后,MK組的游泳不動時間仍長于NS組、C組(P0.05);而MK+RIS組、MK+D1組、MK+D2組3組的游泳不動時間均短于藥物干預(yù)前(P0.05)和MK組(P0.05或P0.01)。3.Y-迷宮實驗結(jié)果分析藥物干預(yù)前MK組、MK+RIS組、MK+D1組、MK+D2組4組大鼠的Y-迷宮交替百分率低于C組(P0.05)。藥物干預(yù)后,MK組的交替百分率低于NS組、C組(P0.01);而MK+RIS組、MK+D1組、MK+D2組3組的交替百分率則高于藥物干預(yù)前(P0.05或P0.01)和MK組(P0.01)。4.Morris水迷宮實驗結(jié)果分析Morris水迷宮定位航行實驗7天的逃避潛伏期分析顯示,測試日間(P0.01)、處理組間(P0.05)差異均有統(tǒng)計學(xué)意義,兩兩比較表明,MK+D2組與MK組、MK+RIS組、MK+D1組及C組差異有統(tǒng)計學(xué)意義(P0.05或P0.01),且測試第3天處理組間(P0.05),MK+D2組與MK組和C組間(P0.01)差異均有統(tǒng)計學(xué)意義。測試第3天運動路程分析亦顯示處理組間(P0.05),MK+D2組與MK組和C組間(P0.01)差異均有統(tǒng)計學(xué)意義。7天的游泳策略分析顯示各組大鼠的分析策略構(gòu)成比在第1、2、5、7天差異有統(tǒng)計學(xué)意義(P0.05或P0.01)。結(jié)論:對青春期大鼠腹腔注射MK-801可誘導(dǎo)精神分裂癥模型,D-絲氨酸對其擬精神分裂癥的陽性癥狀、陰性癥狀及認知功能缺陷均有改善效果,對其學(xué)習(xí)記憶功能可能存在一定影響。
[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緇，

本文編號：1543103