抑郁大鼠电休克治疗后认知功能与突触可塑性研究  

The study of cognitive function and synaptic plasticity in depressed rats following electroconvulsive shock

作　　者：黎平[1] 郝学超[1] 律峰[1] 魏珂[1] 罗洁[1] 曹俊[1] 董军[1] 闵苏[1] 

机构地区：[1]重庆医科大学附属第一医院麻醉科,重庆400016

出　　处：《中国神经精神疾病杂志》2014年第12期715-720,共6页Chinese Journal of Nervous and Mental Diseases

基　　金：国家临床重点专科建设项目(编号:财社【2011】170号);重庆市医学重点学科建设项目(编号:渝卫科教【2007】2号);重庆市科委自然科学基金(编号:cstc2013jcyj A0433)

摘　　要：目的评价自噬及突触素在抑郁大鼠电休克(electroconvulsive shock,ECS)治疗后认知功能损害中的作用。方法选择抑郁模型大鼠24只,接受行为学实验评估抑郁行为和学习记忆能力后,随机分为ECS组和抑郁组,每组12只。ECS组连续7 d给予ECS处理,抑郁组给予伪ECS处理。干预结束后再次进行行为学实验。之后各组随机选取6只大鼠取脑组织,采用免疫组化法检测海马区自噬标记蛋白Beclin 1和LC3Ⅱ,另外6只取海马组织,采用ELISA法检测突触素含量。结果干预前,两组抑郁行为和学习记忆成绩差异无统计学意义(P>0.05)。干预后,ECS组与抑郁组相比或与自身干预前相比,糖水偏好百分比(68.2%±8.7%)、直立次数(7.0±1.9)和水平活动距离[(569.5±70.0)cm]增加,逃避潜伏期[(21.9±5.3)s]和空间探索时间[(20.5±3.9)s]延长(均P<0.05);而抑郁组干预前后的变化无统计学意义(P>0.05)。与抑郁组相比,ECS组CA1、CA3、DG区和海马旁Beclin 1和LC3Ⅱ蛋白表达均上调(P<0.05),海马区突触素蛋白含量增加(P<0.05)。结论抑郁大鼠ECS治疗后认知功能损害与ECS激活海马区自噬增加突触素表达有关。Objective To investigate the role of autophagy and synaptophysin （SYP） in cognitive impairment in de？pressed rats receiving electroconvulsive shock （ECS）. Methods Clean and healthy adult male Sprague-Dawley rats were acclimatized to a standard laboratory environment for 7 days. The chronic unpredictable mild stress （CUMS） was used to establish the rat model of depression. Behavior tests were conducted before and after CUMS to evaluate the depression and cognition level of rats. After establishment of the model, 24 rats were randomly divided into ESC group （group E） and depression group （group D） with 12 rats in each group. The rats in group E were administered 80 mg/kg of propofol （10 mg/mL） by intraperitoneal injection, followed by ECS treatment. The rats in group D were administered propofol by intra？peritoneal injection, followed by sham-ECS treatments. The above interventions were conducted daily for 7 consecutive days. After the interventions, rats underwent behavior tests as before. Subsequently, rats were killed and specimens were collected for measurements. Immunohistochemistry was performed to examine autophagy markers such as Beclin 1 and LC3Ⅱand ELISA was used to detect SYP in the hippocampus. Results Group E after ECS significantly increased the percentage of sucrose preference （68.2%±8.7%）, rearing times （7.0±1.9）, total horizontal distance [（569.5±70.0） cm], es？ cape latency [（21.9±5.3）s] and space exploration time [（20.5±3.9）s] compared with group D or group E before ECS. There was no significant difference in these index between groups before ECS or in group E between before and after ECS（P〉0.05）. Compared with group D, group E had upregulated protein expression levels of Beclin 1 and LC3Ⅱin CA1, CA3, DG as well as the area near the hippocampus and increased SYP contents （P〈0.05）. Conclusions Cognitive impairment in depression rats following ECS correlates with activated autophagy and increased SYP by ECS.

关 键 词：自噬 突触素 抑郁症 电休克治疗 认知功能 

分 类 号：R749.4[医药卫生—神经病学与精神病学]