异丙酚对抑郁大鼠电休克治疗后海马神经元自噬的影响  

Effect of propofol on autophagy in hippocampal neurons of mentally depressed rats after electroconvulsive therapy

作　　者：郝学超[1] 闵苏[1] 黎平[1] 朱贤林[1] 律峰[1] 罗洁[1] 魏珂[1] 谢飞[1] 

机构地区：[1]重庆医科大学附属第一医院麻醉科,400016

出　　处：《中华麻醉学杂志》2014年第5期545-548,共4页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金面上项目（81271501）;国家临床重点专科建设项目经费资助（财社[2011]170号）;重庆市重点学科建设项目经费资助（渝卫科教[2007]2号）

摘　　要：目的 评价异丙酚对抑郁大鼠电休克治疗后海马神经元自噬的影响.方法 健康成年雄性SD大鼠,2～3月龄,体重200～250 g,采用慢性不可预见性轻度应激法建立抑郁大鼠模型.取模型建立成功的大鼠40只,采用随机数字表法,将其分为4组（n=10）：抑郁组（D组）腹腔注射生理盐水8 ml/kg;异丙酚组（P组）腹腔注射异丙酚80 mg/kg;电休克组（E组）腹腔注射生理盐水8 ml/kg后行电休克;异丙酚联合电休克组（PE组）腹腔注射异丙酚80 mg/kg,待翻正反射消失后行电休克.以上处理1次/d,连续7d.分别于建模前、建模后治疗前及治疗结束后（T1-3）,采用糖水偏好实验评价抑郁状态,采用Morris水迷宫实验测定学习记忆功能.水迷宫实验完成后处死大鼠,取海马,采用免疫组化法检测海马CA1区Beclin-1及LC3-Ⅱ的表达水平.结果 与T1时比较,T2时各组糖水偏好百分比降低（P＜0.01）;与D组比较,E组和PE组T3时糖水偏好百分比升高,逃避潜伏期延长,空间探索时间缩短,海马CA1区Beclin-1和LC3-Ⅱ表达上调（P＜0.01）;与E组比较,PE组T3时逃避潜伏期缩短,空间探索时间延长,海马CA1区Beclin-1和LC3-Ⅱ表达下调（P＜0.01）.结论 异丙酚减轻抑郁大鼠电休克治疗后学习记忆功能损害的机制可能与抑制海马神经元自噬激活有关.Objective To evaluate the effect of propofol on autophagy in hippocampal neurons of mentally depressed rats after electroconvulsive （ECT） therapy.Methods Healthy adult male Sprague-Dawley rats,aged 2-3 months,weighing 200-250 g,were used in this study.Mental depression was induced by exposing the rats to chronic unpredictable mild stress （CUMS）.Forty mentally depressed rats were randomly divided into 4 groups （n =10 each）：depression group （group D）,propofol group （group P）,ECT group （group E）,and propofol ＋ ECT group （group PE）.Groups D and P received intraperitoneal normal saline 8 ml/kg and propofol 80 mg/kg,respectively,once a day for 7 consecutive days.Group E received intraperitoneal normal saline 8 ml/kg once a day for 7 consecutive days and then received ECT once a day for 7 consecutive days.Group PE received intraperitoneal propofol 80 mg/kg and then received ECT once a day for 7 consecutive days after the righting reflex disappeared.Before CUMS,after CUMS （before ECT） and after the end of ECT （T1-3）,sucrose preference test was performed to assess depression,and Morris water maze was performed to assess the learning and memory abilities.The rats were sacrificed after completion of Morris water maze and hippocampi were removed for determination of the expression of Beclin-1 and LC3-Ⅱ in CA1 region.Results Compared with the baseline value at T1,the sucrose preference percentage was significantly decreased at T2 in all the groups.Compared with group D,the sucrose preference percentage was significantly increased,the escape latency was prolonged,space exploration time was shortened,and the expression of Beclin-1 and LC3-Ⅱ in hippocampal CA1 was up-regulated at T3 in E and PE groups.Compared with group E,the escape latency was significantly shortened,space exploration time was prolonged,and the expression of Beclin-1 and LC3-Ⅱ in hippocampal CA1 was down-regulated at T3 in group PE.Conclusion The mechanism by which propofol ameliorates cognitive impairment induced

关 键 词：二异丙酚 抑郁 电惊厥疗法 神经元 自噬 

分 类 号：R614[医药卫生—麻醉学]