海马γ-氨基丁酸A型受体α5亚单位在丙泊酚促进恐惧记忆消退机制中的作用  

Role of hippocampal γ-aminobutyric acid type A receptor α5 subunit in fear memory extinction induced by propofol

作　　者：康瑜[1] 唐玲[1] 于布为[1] 薛庆生[1] KANG Yu TANG Ling YU Buwei XUE Qingsheng(Department of Anesthesiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, Chin)

机构地区：[1]上海交通大学医学院附属瑞金医院麻醉科,上海200025

出　　处：《上海医学》2016年第10期608-611,共4页Shanghai Medical Journal

摘　　要：目的检测丙泊酚对小鼠恐惧记忆消退的影响,探讨调控神经细胞再生的海马γ-氨基丁酸A型受体(GABA_A受体)α5亚单位在丙泊酚促进恐惧记忆消退机制中可能的作用。方法将36只C57BL/6小鼠随机分入电刺激丙泊酚组、电刺激对照组和空白对照组,每组12只。应用条件恐惧实验建立小鼠恐惧记忆研究模型。在记忆的巩固期,电刺激丙泊酚组小鼠予腹腔内注射丙泊酚150 mg/kg,电刺激对照组小鼠予腹腔内注射相同体积的0.9%氯化钠溶液,空白对照组完成相同训练流程但不予声音和电刺激。在条件恐惧实验结束后1和4周进行恐惧记忆测试(包括情景测试和声音测试),在条件恐惧实验后1周进行高架十字迷宫测试,检测小鼠的焦虑样行为。第4周恐惧记忆测试后,采用Western印迹法检测小鼠海马区GABA_A受体α5亚单位蛋白质相对表达量。结果在条件恐惧实验结束后1和4周的情景测试中,以及在条件恐惧实验结束后1周的声音测试中,电刺激对照组和电刺激丙泊酚组的木僵时间均显著长于空白对照组(P值均<0.05),电刺激对照组又显著长于电刺激丙泊酚组(P值均<0.05);在条件恐惧实验结束后4周的声音测试中,电刺激对照组和电刺激丙泊酚组的木僵时间均显著长于空白对照组(P值均<0.05),但电刺激对照组与电刺激丙泊酚组间的差异无统计学意义(P>0.05)。在高架十字迷宫测试中,3组小鼠的开放臂停留时间比和开放臂进入次数比的差异均无统计学意义(P值均>0.05)。电刺激对照组的GABA_A受体α5亚单位蛋白质相对表达量显著低于电刺激丙泊酚组和空白对照组(P值均<0.05),后两组间的差异无统计学意义(P>0.05)。结论在恐惧记忆巩固期给予丙泊酚能够促进恐惧记忆的消退,这一作用可能是通过丙泊酚抑制海马GABA_A受体α5亚单位表达降低实现的。Objective To explore the effect of propofol on the fade of fear memory in post-traumatic stress disorder （PTSD） mice models, and the role of hippocampal y-aminobutyric acid type A receptor （GABAA receptor） a5 subunit in the procedure. Methods Thirty-six 057BL/6 mice were divided into three groups （n = 12）= treatment group （propofol anesthesia after shock of PTSD）, control group （normal saline application after shock of PTSD）, and sham group （without shock）. Fear conditioning experiment was used to establish PTSD mouse models. During the fear memory consolidation phase after fear shock, propofol （150 mg/kg） and normal saline were intraperitoneally infused in the treatment group and control group, respectively. The fear memory of context and tone was tested and compared at one week and four weeks after shock. One week after shock, elevated plus maze was performed to test the changes of anxiety mood of mice. Four weeks after shock, the expression of hippocampal GABAA receptor a5 subunit was tested by Western Blotting. Results One week after shock, stupor time in the control group and treatment group were significantly longer than that of sham group both in context test and in tone test （all P〈0.05） moreover, the stupor time in the control group was longer than those of treatment group （both P〈0.05）. Four weeks after shock, the stupor time in the treatment group was decreased when compared with the control group （P〈0.05）, and still longer than that of sham group in the context test （P〈0.05） but no significant difference was found in the stupor time between treatment group and control group inthe tone test （P〉0.05）. There was no significant difference in the ratio of open arm time or open arm entry among the three groups （all P〉0. 05）. The expression of hippocampal GABAA receptor a5 subunit in the control group was significantly lower than those of treatment group and sham group （both P〈0.05）, while the expression in the treatment group had no dif

关 键 词：丙泊酚 y-氨基丁酸A型受体a5亚单位 恐惧记忆 

分 类 号：R614[医药卫生—麻醉学]