CAJ | 학술논문

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.
목적 평개이병분대억욱대서전휴극치료후해마신경원자서적영향.방법 건강성년웅성SD대서,2～3월령,체중200～250 g,채용만성불가예견성경도응격법건립억욱대서모형.취모형건립성공적대서40지,채용수궤수자표법,장기분위4조(n=10):억욱조(D조)복강주사생리염수8 ml/kg;이병분조(P조)복강주사이병분80 mg/kg;전휴극조(E조)복강주사생리염수8 ml/kg후행전휴극;이병분연합전휴극조(PE조)복강주사이병분80 mg/kg,대번정반사소실후행전휴극.이상처리1차/d,련속7d.분별우건모전、건모후치료전급치료결속후(T1-3),채용당수편호실험평개억욱상태,채용Morris수미궁실험측정학습기억공능.수미궁실험완성후처사대서,취해마,채용면역조화법검측해마CA1구Beclin-1급LC3-Ⅱ적표체수평.결과 여T1시비교,T2시각조당수편호백분비강저(P＜0.01);여D조비교,E조화PE조T3시당수편호백분비승고,도피잠복기연장,공간탐색시간축단,해마CA1구Beclin-1화LC3-Ⅱ표체상조(P＜0.01);여E조비교,PE조T3시도피잠복기축단,공간탐색시간연장,해마CA1구Beclin-1화LC3-Ⅱ표체하조(P＜0.01).결론 이병분감경억욱대서전휴극치료후학습기억공능손해적궤제가능여억제해마신경원자서격활유관.
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 by ECT may be related to inhibition of activation of autophagy in hippocampal neurons of mentally depressed rats.