摘要
目的观察抑郁大鼠无抽搐电休克治疗(MECT)后海马内谷氨酸脱羧酶-65(GAD65)的表达以及γ-氨基丁酸(GABA)含量的变化,并阻断γ-氨基丁酸A型受体(GABAA),探讨MECT治疗抑郁症与GABA通路的关系。方法48只SD大鼠随机分为MECT治疗组(治疗组)、GABAA受体拮抗组(拮抗组)、抑郁模型对照组(模型组)、空白对照组(对照组),每组12只。前3组大鼠采用孤养加慢性轻度不可预见性应激建立抑郁模型,治疗组和拮抗组均隔天给予MECT处理6次,但后者在丙泊酚腹腔注射麻醉时同时注射GABAA受体特异性阻断剂荷包牡丹碱,余2组正常饲养。随后行open-field评分,每组随机抽取6只大鼠以免疫组织化学法检测海马GAD65蛋白的表达,其余6只以高效液相色谱法分析海马GABA含量。结果①open-field评分:电休克处理后,治疗组和拮抗组水平计分、垂直计分均高于模型组(P<0.05),拮抗组低于治疗组(P<0.05),提示电休克可有效缓解大鼠抑郁状态,阻断GABAA受体可减弱电休克疗效。②GAD65表达、GABA含量:模型组GAD65的表达量、GABA含量低于对照组(P<0.05),治疗组、拮抗组大鼠高于模型组(P<0.05),提示电休克可以上调GAD65表达,升高GABA含量。结论无抽搐电休克可上调抑郁大鼠海马GAD65表达,升高GABA含量,改善抑郁症状,GABA通路可能部分参与了无抽搐电休克治疗抑郁症的机制。
Objective To investigate the effects of modified electroconvulsive therapy （MECT） on the expression of gamma-aminobutyric acid （GABA） and GAD65 in the hippocampus of depressed rats and explore the possible involvement of GABA pathway. Methods Forty eight SI） rats were randomly divided into 4 groups （ n = 12 ） ： MECT group （ M）, GABAA -block group （B） , depression group （D） and control group （C）. Mental depression model was established in group M, B and D by subjecting the animals to separation and chronic unpredictable mild stress. The animals in both group M and group B received MECT with propofol （ 100 mg/kg, i. p. ） on alternate days for 6 times and the latter also received extra bicuculline （5 mg/kg, i. p. ） in MECT. The behavior of the animals was evaluated by open-field test. Six animals in each group were randomly selected for determination of the GABA and expression of GAD65 in the hippocampus by high performance liquid chromatography （HPLC） and immunohistochemistry, respectively. Results The scores of open-field test were significantly increased in both group M and B（P 〈0. 05 ）compared with group D. The scores of open-field test were significantly higher in group M than in group B（P 〈0. 05）. The GABA and expression of GAD65 were significantly increased in group M and B compared with group D （P 〈 0. 05 ）. Conclusions MECT can up-regulate GABA and the expression of GAD65 and improve the symptoms of depression which is mediated partially through GABA pathway.
出处
《中国神经精神疾病杂志》
CAS
CSCD
北大核心
2009年第4期238-241,共4页
Chinese Journal of Nervous and Mental Diseases
