CAJ | 학술논문

目的评价丙泊酚对抑郁大鼠电休克治疗(ECT)后海马神经元型一氧化氮合酶(nNOS)活性及其羧基末端PDZ结构的接头蛋白(CAPON)表达的影响.方法清洁级成年雄性SD大鼠,体重200 ～ 250 g,2～3月龄,采用慢性轻度不可预见性应激法建立抑郁模型.选建模成功的大鼠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;单纯丙泊酚组(DP组)腹腔注射丙泊酚80 mg/kg；单纯ECT组(DE组)腹腔注射生理盐水8 ml/kg后实施ECT;丙泊酚+ECT组(DPE组)腹腔注射丙泊酚80mg/kg待翻正反射消失后实施ECT.以上处理1次/d,连续7d.于建模前、建模后、治疗结束后采用糖水偏好实验评价大鼠抑郁状态,采用Morris水迷宫实验测定学习记忆能力.水迷宫实验结束后采用免疫组化法检测海马神经元nNOS及CAPON的表达.结果与D组比较,DE组、DPE组糖水偏好比升高,DE组逃避潜伏期延长,空间探索时间缩短,DP组海马DG区、CA1区和CA3区神经元nNOS和CAPON表达下调,DE组海马DG区、CA1区和CA3区神经元nNOS表达上调、CAPON表达下调(P＜0.05)；与DE组比较,DPE组逃避潜伏期缩短,空间探索时间延长,海马DG区、CA1区和CA3区神经元nNOS表达下调、CAPON表达上调(P＜0.05).结论丙泊酚减轻抑郁大鼠电休克治疗后认知功能损害的机制可能与其抑制海马神经元nNOS活性和上调CAPON表达有关.
목적 평개병박분대억욱대서전휴극치료(ECT)후해마신경원형일양화담합매(nNOS)활성급기최기말단PDZ결구적접두단백(CAPON)표체적영향.방법 청길급성년웅성SD대서,체중200 ～ 250 g,2～3월령,채용만성경도불가예견성응격법건립억욱모형.선건모성공적대서40지,채용수궤수자표법,장기분위4조(n=10):억욱조(D조)복강주사생리염수8 ml/kg;단순병박분조(DP조)복강주사병박분80 mg/kg；단순ECT조(DE조)복강주사생리염수8 ml/kg후실시ECT;병박분+ECT조(DPE조)복강주사병박분80mg/kg대번정반사소실후실시ECT.이상처리1차/d,련속7d.우건모전、건모후、치료결속후채용당수편호실험평개대서억욱상태,채용Morris수미궁실험측정학습기억능력.수미궁실험결속후채용면역조화법검측해마신경원nNOS급CAPON적표체.결과 여D조비교,DE조、DPE조당수편호비승고,DE조도피잠복기연장,공간탐색시간축단,DP조해마DG구、CA1구화CA3구신경원nNOS화CAPON표체하조,DE조해마DG구、CA1구화CA3구신경원nNOS표체상조、CAPON표체하조(P＜0.05)；여DE조비교,DPE조도피잠복기축단,공간탐색시간연장,해마DG구、CA1구화CA3구신경원nNOS표체하조、CAPON표체상조(P＜0.05).결론 병박분감경억욱대서전휴극치료후인지공능손해적궤제가능여기억제해마신경원nNOS활성화상조CAPON표체유관.
Objective To evaluate the effects of propofol on neuronal nitric oxide synthase (nNOS) activity and carboxy-terminal PDZ ligand of nNOS (CAPON) expression in hippocampal neurons after electroconvulsive therapy (ECT) in mentally depressed rats.Methods Healthy adult male Sprague-Dawley rats,aged 2-3 months,weighing 200-250 g,were used in this study.Mentally 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):mental depression group (group D),propofol group (group DP),ECT group (group DE),and propofol +ECT group (DPE group).Groups D and DE received intraperitoneal normal saline 8 ml/kg,and in addition group DE received ECT once a day for 7 consecutive days.Groups DP and DPE received intraperitoneal propofol 80 mg/kg,and in addition after the righting reflex disappeared,group DPE received ECT once a day for 7 consecutive days.All rats underwent sucrose preference test and Morris water maze test before CUMS,after CUMS,and after the end of treatment.The rats were sacrificed after completion of Morris water maze test and hippocampi were removed for determination of nNOS and CAPON expression in hippocampal neurons.Results Compared with group D,the sucrose preference percentage was significantly increased in DE and DPE groups,the escape latency was prolonged and space exploration time was shortened,the expression of nNOS in hippocampal DG,CA1 and CA3 regions was up-regulated and the expression of CAPON in hippocampal DG,CA1 and CA3 regions was down-regulated in group DE,and the expression of nNOS and CAPON in hippocampal DG,CA1 and CA3 regions was downregulated in group DP (P ＜ 0.05).Compared with group DE,the escape latency was significantly shortened and space exploration time was prolonged,the expression of nNOS in hippocampal DG,CA1 and CA3 regions was down-regulated and the expression of CAPON in hippocampal DG,CA1 and CA3 regions was up-regulated in group DPE (P ＜ 0.05).Conclusion The mechanism by which propofol reduces the cognitive impairment induced by ECT in mentally depressed rats is related to inhibition of nNOS activity and up-regulation of CAPON expression in hippocampal neurons.