小剂量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1和γ-氨基丁酸A受体表达的影响

Effect of low-dose ketamine combined with propofol anesthesia on expression of GluR1 and GABAA R in hippocampus after electroconvulsive therapy in depressed rats

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（ECT）后海马谷氨酸受体1（GluR1）和γ-氨基丁酸A受体（GABAA R）表达的影响.方法 SPF级成年雄性SD大鼠50只,体重200～250 g,2～3月龄,采用慢性不可预见性轻度应激法建立抑郁模型.采用随机数字表法,将其分为5组（n=10）：抑郁组（D组）、ECT组、氯胺酮＋ECT组（KE组）、异丙酚＋ECT组（PE组）和氯胺酮＋异丙酚＋ ECT组（KPE组）.ECT组腹腔注射生理盐水8 ml/kg后实施ECT（电流50 mA、频率50 Hz、正弦波、脉冲宽度0.7 ms、持续1 s）,以引起强直-阵挛抽搐发作为处理成功;KE组、PE组分别腹腔注射氯胺酮10 mg/kg和异丙酚100 mg/kg,KPE组腹腔注射氯胺酮10 mg/kg与异丙酚80 mg/kg,待大鼠翻正反射消失后行ECT,参数设置同ECT组,ECT为1次/d,连续7d.分别于建模前、建模后1d、治疗结束后1d行糖水消耗（SFC）实验.取大鼠海马组织,采用免疫组化法测定GluR1及GABAA R的表达水平,并计算GluR1/GABAA R比值.结果 与D组比较,其余4组治疗结束后1 d SFC百分比升高,海马CA1区和CA3区GluR1表达上调,GluR1/GABAA R比值升高,ECT组、PE组和KPE组海马CA1区和CA3区GABAA R表达下调（P＜0.05）;与ECT组比较,KPE组治疗结束后1 d SFC百分比升高,海马CA1区和CA3区GABAA R和GluR1表达上调,GluR1/GABAA R比值升高,KE组海马CA1区和CA3区GABAA R和GluR1表达上调,PE组海马CA1区和CA3区GABAA R表达下调（P＜0.05）;与PE组比较,KPE组治疗结束后1 d SFC百分比升高,海马CA1区和CA3区GABAA R和GluR1表达上调,GluR1/GABAA R比值升高（P＜0.05）.结论 小剂量氯胺酮复合异丙酚增强ECT对抑郁大鼠疗效的机制可能与更好地调节海马GluR1与GABAA R平衡有关.

Objective To evaluate the effects of low-dose ketamine combined with propofol anesthesia on the expression of glutamate receptor 1 （GluR1） and γ-aminobutyric acid type A receptor （GABAA R） in hippocampus after electroconvulsive therapy （ECT） in depressed rats.Methods Fifty healthy adult male SpragueDawley rats,aged 2-3 months,weighing 200-250 g,were used in this study.The depressed model was induced by chronic unpredictable mild stress （CUMS）.The mentally depressed rats were randomly divided into 5 groups （n =10 each）：depression group （group D）,ECT group,ketamine ＋ ECT group （group KE）,propofol ＋ ECTgroup （group PE） and ketamine ＋ propofol ＋ ECT group （group KPE）.Group ECT received ECT once a day for 7 consecutive days after intraperitoneal injection of normal saline 8 ml/kg.KE,PEK and KPE groups received ECT once a day for 7 consecutive days after intraperitoneal injection of ketamine 10 mg/kg,propofol 100 mg/kg,and ketamine 10 mg/kg ＋ propofol 80 mg/kg,respectively.Sucrose fluid consumption was performed before CUMS,at 1 day after CUMS and at 1 day after ECT.The rats were sacrificed and hippocampi were removed for determination of the expression of GluR1 and GABAA R （by immuno-histochemistry）.The GluR1/GABAA R ratio was calculated.Results Compared with group D,the sucrose consumption percentage was significantly increased at 1 day after ECT,the expression of GluR1 in hippocampal CA1 and CA3 regions was up-regulated,and the GluR1/GABAA Rratio was increased in the other four groups,and the expression of GABAA R in hippocampal CA1 and CA3 regions was down-regulated in ECT,PE and KPE groups （P 〈 0.05）.Compared with ECT group,the sucrose consumption percentage was significantly increased at 1 day after ECT,the expression of GABAA R and GluR1 in hippocampal CA1 and CA3 regions was up-regulated,and the GluR1/GABAA R ratio was increased in KPE group,the expression of GluR1 and GABAA R in hippocampal CA1 and CA3 regions was up-regulated in KE group,and the expression of GABAA R in hippocampal CA1 and CA3 regions was down-regulated in PE group （P 〈 0.05）.Compared with group PE,the sucrose consumption percentage was significantly increased at 1 day after ECT,the expression of GluR1 and GABAAR in hippocampal CA1 and CA3 regions was up-regulated,and the GluR1/GABAA R ratio was increased in KPE group （P 〈 0.05）.Conclusion The mechanism by which low-dose ketamine combined with propofol enhances the efficacy of ECT in depressed rats may be related to better regulation of the balance between hippocampal GluR1 and GABAA R.