氯胺酮复合异丙酚麻醉对抑郁大鼠电休克后海马谷氨酸受体亚基1和亚基2的影响  

Effect of ketamine combined with propofol anesthesia on expression of glutamine receptor subunit 1 and 2 in the hippocampus of depressed rats after electroconvulsive therapy

作　　者：秦珮珮 闵苏[1] 张帆[1] 任力[1] 郝学超[1] 朱贤林[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》2015年第9期523-529,共7页Chinese Journal of Nervous and Mental Diseases

基　　金：国家自然科学基金面上项目(编号:81271501);国家临床重点专科建设项目经费资助(编号:财社(2011)170号);重庆市科委应用开发项目经费资助(编号:cstc2014yykf A110028)

摘　　要：目的评价小剂量氯胺酮复合异丙酚麻醉对抑郁大鼠电休克(electroconvulsive therapy,ECT)后海马谷氨酸受体亚基1(glutamate receptor subunit 1,Glu R1)及亚基2(glutamate receptor subunit 2,Glu R2)的影响。方法健康成年雄性SD大鼠32只,采用孤养与慢性轻度不可预见性应激(chronic unpredictable mild stress,CUMS)建立抑郁模型,建模成功后随机分为抑郁组(A组)、ECT组(B组)、ECT+异丙酚组(C组)和ECT+异丙酚+氯胺酮组(D组)4组,每组8只;另取8只正常大鼠作为对照组。对照组不做任何处理;A组腹腔注射生理盐水8 m L/kg后给予伪ECT处理;B、C、D组分别腹腔注射生理盐水8 m L/kg、异丙酚80 mg/kg、异丙酚80 mg/kg+氯胺酮10 mg/kg后行ECT处理,上述处理连续7 d。分别采用糖水偏好实验和Morris水迷宫实验评价大鼠抑郁状态和学习记忆功能,Western-blot及RT-PCR检测大鼠海马Glu R1和Glu R2及其m RNA表达。结果 ECT处理后,B、C、D组糖水偏好百分比变化均较A组和对照组明显,其中D组升高最为明显(均P<0.05);B组逃避潜伏期延长且变化值与其他组均具有统计学差异,而D组逃避潜伏期缩短最为明显,其次为A组(均P<0.05);B组空间探索时间缩短且变化值均大于其他组,D组空间探索时间延长最为明显(均P<0.05)。ECT处理后,B、C、D组Glu R1表达较A组高,其中D组最高(均P<0.05);Glu R1m RNA表达在组间无统计学差异B、C组Glu R2及其m RNA表达较其余组低,其中B组最低(均P<0.05),A、D组和对照组间Glu R2及其m RNA差异无统计学意义(P>0.05)。结论小剂量氯胺酮复合异丙酚麻醉在协同ECT抗抑郁效果的同时,能够更大程度地改善ECT后学习记忆功能,其机制可能与上调海马Glu R1和Glu R2表达相关。ObjectiveTo explore the effect of low-dose ketamine combined with propofol anesthesia on expression of glutamine receptor subunit 1（Glu R1） and 2（Glu R2） in the hippocampus of depressed rats after electroconvulsive therapy.MethodsHealthy adult male Sprague-Dawley rats, weighing 200~250 g, were used in this study. Mental depression was induced by chronic unpredictable mild stress. Thirty-two depressed rats were randomly divided into 4 groups（n=8）： metal depression group（group A）, ECT group（group B）, ECT＋propofol group（group C） and ECT＋propofol＋ketamine group（group D）. Eight normal rats served as control group. Control group received no treatment. Group A receivedintraperitoneal injection of normal saline 8 m L/kg plus sham ECT. Group B, C and D received ECT once a day for 7 consecutive days following intraperitoneal injection of normal saline 8 m L/kg, propofol 80 mg/kg and propofol 80 mg/kg ＋ketamine 10mg/kg, respectively. Sucrose preference test and Morris water maze were performed to assess depressed behavior and learning and memory function, respectively. RT-PCR and Western-blot assay were used to detect the expression of Glu R1, Glu R2 and their m RNA expression.ResultsAfter ECT, compared with control group and group A, changes of SPP in group B, C and D were obvious. The change of SPP in group D was much higher than all other groups（P 0.05）. Rats in group B showed prolonged escape latency and shortened space exploration time, which were significantly different from all other groups（P 0.05）. Rats in group D showed the most shortened escape latency and prolonged space exploration time（P 0.05）. The expression of Glu R1 was significantly increased in group B, C and D compared with group A（P 0.05）. The expression of Glu R2 and m RNA was significantly decreased in group B and C（P 0.05）. The difference in Glu R2 and m RNA expression was not significant among group A, D and control group（P 0.05）.Conclusion Low-dose ketamine combined with propofol anesthes

关 键 词：抑郁 电休克 异丙酚 氯胺酮 谷氨酸受体 

分 类 号：R614[医药卫生—麻醉学]