不同剂量异丙酚复合电休克治疗对抑郁大鼠行为学及海马突触素的影响

1、不同剂量异丙酚复合电休克治疗对抑郁大不同剂量异丙酚复合电休克治疗对抑郁大鼠行为学及海马突触素的影响鼠行为学及海马突触素的影响重庆医科大学附属第一医院麻醉科 400016刘媛媛 闵苏 董军 曹俊 黎平 刘永峰【摘要摘要】 目的目的 探讨不同剂量异丙酚复合电休克治疗对抑郁大鼠行为学改变及海马突触素( SYP )表达的影响。 方法方法 成年健康雄性 SD 大鼠 50 只，体重200250 g，随机分为 5 组( n=10 )：正常对照组( C 组)、抑郁组( D 组)以及不同剂量异丙酚联合电休克组，其中包括低剂量组( M1 组)、中剂量组( M2 组)、高剂量组( M3 组)。采用孤养加慢性不可预见

2、轻度应激( CUMS )建立抑郁模型，建模成功后，C 组、D 组腹腔注射生理盐水 10 ml/kg，于大鼠双颞侧安放电极但不实施电休克处理，M1、M2、M3 组分别腹腔注射异丙酚 90 mg/kg、110 mg/kg、130 mg/kg，待翻正反射消失后，将电极安放于大鼠双颞侧，行电休克处理( 50 mA、50 Hz、单个正弦半波刺激 20 ms、持续 50 次 )，引起强直-阵挛抽搐发作。以上处理每天一次，连续 7 d，一共 7 次。建模前后及处理后 1 天均对大鼠进行 open field 测试和糖水消耗实验。测试结束后 1 天内处死大鼠，采用免疫组织化学法检测大鼠海马 CA3 区 SYP

3、 蛋白的表达，RT-PCR 法检测大鼠海马 SYP mRNA 的相对表达量。结果结果 建模后，与 C 组比较，其余 4 组水平计分、垂直计分、理毛次数减少，中央格停留时间延长，糖水消耗百分比下降( P0.05 )。电休克治疗后，与 D 组比较，M1、M2 组水平计分、垂直计分、理毛次数增加，中央格停留时间减少，糖水消耗百分比升高，SYP 蛋白及其 mRNA 表达水平升高( P0.05 )，M3 组各项行为学评分与 SYP 表达差异均无统计学意义( P0.05 )；与 M1 组比较，M3 组水平计分、垂直计分、理毛次数减少，中央格停留时间增加，SYP 蛋白及其 mRNA 表达水平降低( P0.0

4、5 )。结论结论 90 mg/kg、110 mg/kg 异丙酚复合电休克治疗对抑郁大鼠有一定疗效，而 130 mg/ kg 异丙酚复合电休克治疗对抑郁大鼠的疗效不佳，其机制可能与大剂量异丙酚过度抑制大鼠电休克后海马 SYP 表达有关。【关键词关键词】二二异丙酚；电惊厥疗法；抑郁症；突触素 EffectEffect ofof differentdifferent dosesdoses ofof propofolpropofol onon ethologyethology andand synaptophysinsynaptophysin inin hippocamhippocam puspus

5、ofof depresseddepressed ratsrats afterafter electroconvulsiveelectroconvulsive therapytherapy LIU Yuan-yuan, MIN Su, DONG Jun, et al. Department of Anesthesiology, First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China Corresponding author : MIN Su(E-mail:)AbstractAbstrac

6、t ObjectiveObjective To investigate the effect of different doses of propofol on ethology and the expression of mRNA and protein of synaptophysin( SYP ) in hippocampus of depressed rats after electroconvulsive therapy( ECT ). MethodsMethods Fifty adult male SD rats weighing 200250 g were randomly di

7、vided into five groups (n=10 each): one control group (C) , one mental depression group (D) and three different doses of propofol combined with electroconvulsive therapy group ( M1, M2, M3 ). Chronic unpredictable mild stress ( CUMS ) model was established in groups except group C. The rats in group

8、 M1, M2 and M3 received intraperitoneal ( IP ) propofol 90、110 and 130 mg/kg respectively + ECT once a day for 7 times, whereas the rats in group C and D received IP normal saline instead of propofol. The rats underwent open field test and sucrose liquid consumption test the day before and after CUM

9、S model established and one day after treatment. The rats were killed within 24h after the last test for determination of the expression of SYP protein ( using immuno-histochemistry ) and mRNA ( using RT-PCR ) in the hippocampus. ResultsResults The ambulation scores, rearing scores, grooming times a

10、nd sucrose consump tion percentage were significantly decreased while the center grid detention time ( CDT ) was significantly increased in other groups as compared with group C after model established. The ambulation scores, rearing scores, grooming times , sucrose consumption percentage, SYP prote

11、in and mRNA expression were significantly increased while CDT was significantly decreased in group M1 and M2 as compared with group D. The ambulation scores, rearing scores, grooming times, sucrose consumption percentage, SYP protein and mRNA expression were significan tly decreased while CDT was significantly increased in group M3 as compared with group M1. ConclusionConclusion 90 mg/kg、110 mg/kg propofol combined with ECT have therapeutic effect to depressed rats, whereas 130 mg/ kg propofol combined with ECT do not, which may due to hig