长春西汀对抑郁大鼠MECT后学习记忆障碍的改善作用机制  

Action mechanism of vinpocetine in improving learning and memory disorders in depressive rats after MECT

作　　者：鄢传东 王鹏[1,2] 房茂胜 YAN Chuandong;WANG Peng;FANG Maosheng(Wuhan Mental Health Center,Wuhan Psychological Hospital,Wuhan 430000,China;Early Intervention Ward,Wuhan Psychological Hospital,Wuhan 430000,China)

机构地区：[1]武汉市精神卫生中心 [2]武汉市心理医院早期干预病区,湖北武汉430000

出　　处：《西安交通大学学报（医学版）》2023年第6期873-879,共7页Journal of Xi’an Jiaotong University（Medical Sciences）

基　　金：湖北省卫生健康委员会科研项目(No.WJ2019M016);国家自然科学基金资助项目(No.81771445)。

摘　　要：目的探究长春西汀对抑郁大鼠无抽搐电休克(MECT)后学习记忆障碍的改善作用机制。方法采用慢性温和不可预见性应激(CUMS)法构建抑郁症大鼠模型,将30只抑郁症大鼠随机分为抑郁组、MECT组、MECT+长春西汀(10 mg/kg)组,每组10只,另选取10只未处理的健康大鼠作对照组。采用Morris水迷宫实验和新物体识别实验检测学习记忆能力,糖度偏好实验评估抑郁状态,制备海马脑片进行电生理实验,高尔基染色检测树突棘密度,qPCR和Western blotting实验检测内源性大麻素相关基因[二酰基甘油脂肪酶(DAGLα)、单酰甘油脂肪酶(MAGL)和内源性大麻素Ⅰ型受体(CB1R)]表达。此外注射慢病毒下调海马中CB1R和DAGLα表达,再次建模与处理后,进行行为学检测。结果与对照组比较,抑郁组糖度偏好、空间探索时间、相对辨别指数、长时程增强(LTP)、树突棘密度、DAGLα和CB1R表达降低,逃避潜伏期和MAGL表达升高(P<0.05);与抑郁组比较,MECT组糖度偏好、逃避潜伏期和MAGL表达升高,空间探索时间、相对辨别指数、LTP、树突棘密度、DAGLα和CB1R表达降低(P<0.05),MECT+长春西汀组糖度偏好、空间探索时间、相对辨别指数、LTP、树突棘密度、DAGLα和CB1R表达升高,逃避潜伏期和MAGL表达降低(P<0.05);与MECT组比较,MECT+长春西汀组糖度偏好、空间探索时间、相对辨别指数、LTP、树突棘密度、DAGLα和CB1R表达升高,逃避潜伏期和MAGL表达降低(P<0.05);慢病毒下调DAGLα或CB1R表达后,可抑制长春西汀对抑郁大鼠MECT治疗后行为学表现的改善作用。结论长春西汀可明显改善抑郁大鼠MECT治疗后的学习记忆障碍,可能与调节内源性大麻素相关基因表达、增强突触可塑性有关。Objective To explore the action mechanism of vinpocetine in improving learning and memory disorders in depressive rats after modified electroconvulsive therapy(MECT).Methods The models of depressive rats were constructed by chronic unpredictable mild stress(CUMS)method.A total of 30 rats with depression were randomly divided into depression group,MECT group,and MECT+vinpocetine(10 mg/kg)group,with 10 in each group.A total of 10 untreated healthy rats were enrolled as control group.The learning and memory ability were tested by Morris water maze test and novel object recognition test.The depression state was evaluated by sugar preference test.The brain slices of the hippocampus were prepared for electrophysiological experiments.The density of dendritic spine was detected by Golgi staining.The expressions of endocannabinoids related genes[diacylglycerol lipase(DAGLα),monoacylglycerol lipase(MAGL),and endocannabinoid type-I receptor(CB1R)]were detected by qPCR and Western blotting.The lentivirus was injected to downregulate the expressions of CB1R and DAGLαin the hippocampus.After re-modeling and treatment,behavioral tests were performed.Results Compared with control group,sugar preference,spatial exploration time,relative discrimination index,long-term potentiation(LTP),density of dendritic spine,expressions of DAGLαand CB1R were decreased,while escape latency and MAGL were increased in depression group(P<0.05).Compared with depression group,sugar preference,escape latency,and MAGL were increased,while spatial exploration time,relative discrimination index,LTP,density of dendritic spine,expressions of DAGLαand CB1R were decreased in MECT group(P<0.05).Compared with depression group,sugar preference,spatial exploration time,relative discrimination index,LTP,density of dendritic spine,expressions of DAGLαand CB1R were increased,while escape latency and MAGL were decreased in MECT+vinpocetine group(P<0.05).Compared with MECT group,sugar preference,spatial exploration time,relative discrimination index,LTP,density

关 键 词：长春西汀 抑郁 无抽搐电休克 学习记忆障碍 内源性大麻素 突触可塑性 

分 类 号：R749.1[医药卫生—神经病学与精神病学]