异丙酚预先给药对抑郁大鼠电休克后海马Glu和GABA水平的影响

目的 探讨异丙酚预先给药对抑郁大鼠电休克后海马Glu和GABA水平的影响.方法 雄性SD大鼠30只,2～3月龄,体重200～250 g,随机分为5组(n=6):正常对照组(C组)、抑郁组(D组)、异丙酚组(P组)、电休克组(E组)、异丙酚+电休克组(PE组).采用孤养加慢性不可预见性应激法建立抑郁模型,建模后C组和D组腹腔注射生理盐水3 ml,P组腹腔注射异丙酚100 mg/kg,3组均不行电刺激;E组和PE组分别腹腔注射生理盐水3 ml或异丙酚100 mg/kg后行电休克治疗(频率50 Hz、电流50 mA、持续时间20 ms).各组处理隔日1次.共6次.于建模前1天(基础状态),建模后第1天(T1)及处理后第2天(T2)采用Open-field法行行为学评分.于T1.2时采用Morris水迷宫检测学习记忆功能,测定后处死,采用高效液相色谱法分析海马谷氨酸(Glu)、γ-氨基丁酸(GABA)含量,计算Gln/GABA比值.结果 与C组比较,其余4组行为学评分降低,学习记忆功能降低,D组和P组Glu含量升高,GABA含量降低,Glu/GABA比值升高,E组Glu含量降低,GABA含量升高,Glu/GABA比值降低(P<0.05);与D组和P组比较,E组行为学评分升高,学习记忆功能降低,Glu含量降低,GABA含量升高,Glu/GABA比值降低(P<0.05),PE组行为学评分升高,Glu含量降低,GABA含量升高,Glu/GABA比值降低(P<0.05),学习记忆功能差异无统计学意义(P>0.05);与E组比较,PE组学习记忆功能增强,Glu含量升高,GABA含量降低,Glu/GABA比值升高(P<0.05).结论 异丙酚预先给药改善电休克治疗后学习记忆功能的机制可能与异丙酚调节Glu和GABA功能状态的平衡有关.

Effects of propofol pretreatment on the levels of glutamate and gamma-aminobutyric acid in hippocampus of mentally depressed rats after electro-convulsive therapy

Objective To investigate the effects of propofol pretreatment on the levels of glutamate (Glu) and gamma-aminobytyric acid (GABA) in hippocampus of mentally depressed rats after electro-convulsive therapy.Methods Thirty male 2-3 month old SD rats weighing 200-250 g were randomly divided into 5 groups ( n = 6each) : group Ⅰ control (C) ; group Ⅱ mental depression (D) ; group Ⅲ propofol (P) ; group Ⅳ electric shock (E) and groupV propofol + electric shock (PE). Mental depression was induced by subjecting the animals to different kinds of stresses every day for 21 consecutive days in group Ⅱ - Ⅴ. After mental depression had been induced, the animals received intraperitoneal (IP) propofol 100 mg/kg in group P, electric shock in group E and propefol 100 mg/kg + electric shock in group PE respectively once every 2 days × 6 times. The anxiety-related behavior was assessed by open-field test and scored (the higher the score the better) on the day before induction of mental depression was started (To ,baseline), on the 1st day after mental depression had been induced (T1) and on the 2nd day after treatment (T2). The learning ability and memory were evaluated by Morris water maze at T1 and T2. The animals were killed after the last test and their brains were removed and bilateral hippocampi were isolated for determination of glutamate and GABA contents by high performance liquid chromatography (HPLC).Results The behavior scores and learning ability and memory were significandy decreased in group Ⅱ-Ⅴ as compared with the control group (P<0.05). The behavior scores were significandy higher in group E (Ⅳ) and PE (Ⅴ) than ingroup D (Ⅱ) and P (Ⅲ)(P<0.05). The learning ability and memory were significantly better after treatment (T2) in group PE than in group E (P<0.05). The Glu/GABA ratio in hippocampus was significantly higher but GABA content was significantly lower and Glu content was signficantly higher in group D and P than in group C, E and PE (P<0.05). The Glu/GABA ratio was significantly lower but GABA content was significantly higher and Glu content was significantly lower in group E than in group C and PE (P<0.05).Conclusion Propofol pretreatment can improve the learning ability and memory of the mentally depressed rats under electro-convulsive therapy by regulating the balance between Glu and GABA in the brain.