γ-氨基丁酸能神经元在丙泊酚缓解抑郁模型大鼠电休克后脑损伤中的作用

The role of GABAergic neurons in propofol-mediated alleviation of electroconvulsive shock-induced learning and memory impairment in rats with depression after electroshock

目的探讨γ-氨基丁酸(γ-aminobutyric acid,GABA)能神经元在丙泊酚缓解抑郁大鼠电休克(electroconvulsive shock,ECS)后学习记忆损伤中的作用。方法将慢性温和不可预见性应激(chronic unpredictable mild stress,CUMS)法建模成功的36只抑郁症模型大鼠随机分为丙泊酚+电休克组、电休克组和抑郁组,另设同批次未建模的12只健康大鼠为对照组。丙泊酚+电休克组用丙泊酚联合电休克治疗,电休克组行电休克治疗,抑郁组与对照组行伪电休克处理。治疗完毕行Morris水迷宫实验评估大鼠空间学习记忆能力;ELISA法检测海马GABA浓度;免疫组化法和Western-blot检测海马GABAARα5的蛋白表达。结果Morris水迷宫实验结果提示,电休克组逃避潜伏期最长,空间探索时间最短(P<0.05);电休克组和丙泊酚+电休克组比抑郁组逃避潜伏期延长,空间探索时间缩短(P<0.05);与对照组比较,其余各组逃避潜伏期缩短,空间探索时间延长(P<0.05)。蛋白表达方面,与对照组相比,抑郁组GABA含量下降,GABAARα5表达水平降低(P<0.05),电休克组和丙泊酚+电休克组GABA含量和GABAARα5蛋白表达升高(P<0.05);与电休克组相比,丙泊酚+电休克组GABA含量下降,GABAARα5蛋白表达升高(P<0.05)。结论丙泊酚在电休克过程中具有脑保护作用,其机制可能与上调海马GABA能神经系统相关递质和受体的表达有关。

Objective To investigate the role ofγ-aminobutyric acid(GABA)in the learning and memory function by examining the expression of GABA related neurotransmitters and receptors in the hippocampus of depression rats,and to explore the mechanism of propofol in alleviating the learning and memory dysfunction in depressive rats after electroconvulsive shock(ECS).Methods Thirty-six Sprague Dawley(SD)depressed rats induced by chronic unpredictable mild stress(CUMS),were randomly divided into 3 groups(n=12):depression group(group D),ECS treatment group(group ECS)and propofol combined ECS group(group MECT).Twelve normal rats were served as the control group(Group C).Group C and group D received sham ECS after intraperitoneal injection of saline,group ECS received ECS after intraperitoneal injection of saline,and group MECT received propofol after intraperitoneal injection.The depressive behavior and the learning and memory function were assessed by the sucrose preference test(SPT)and Morris water maze,respectively.The GABA levels and protein expression of GABAARα5 of the hippocampus were detected by ELISA,Western-blot and immunohistochemistry,respectively.Results After CUMS,sucrose preference percentage(SPP)was obviously decreased in group D,group ECS and group MECT compared with group C(P<0.05).After different treatment,SPP and space exploration time was decreased and escape latency was increased in group D,group ECS and group MECT compared with group C(P<0.05).SPP and escape latency was increased and space exploration time was decreased in group ECS and group MECT compared with group D(P<0.05).There was no significant difference in SPP between group ECS and group MECT(P>0.05).However,escape latency was shortened and space exploration time was prolonged in group MECT compared with group ECS(P<0.05).Compared with group C,GABA levels and the expression of GABAARα5 were lower in group D(P<0.05)and were higher in group ECS and in group MECT(P<0.05).Compared with group D,GABA and GABAARα5 levels were higher in group ECS and in group MECT(P<0.05).Compared with group ECS,GABA and GABAARα5 levels were higher in group MECT(P<0.05).Conclusion Propofol has neuroprotective effects during ECS in depressive rats possibly through upregulation of GABAergic neurotransmitter and receptor expression in rat hippocampus.