Ⅰ型促代谢性谷氨酸受体在小剂量氯胺酮保护抑郁大鼠电休克后学习记忆功能中的作用

doi:10.3969/j.issn.1674-8115.2019.11.006

上海交通大学学报（医学版） ›› 2019, Vol. 39 ›› Issue (11): 1248-.doi: 10.3969/j.issn.1674-8115.2019.11.006

Ⅰ型促代谢性谷氨酸受体在小剂量氯胺酮保护抑郁大鼠电休克后学习记忆功能中的作用

刘大为1，任力2，闵苏2

1. 重庆医科大学附属永川医院麻醉科，重庆 402160；2. 重庆医科大学附属第一医院麻醉科，重庆 400016

出版日期:2019-11-28 发布日期:2019-12-16
通讯作者: 闵苏，电子信箱：ms89011068@163.com。
作者简介:刘大为（1988—），男，主治医师，硕士生；电子信箱：136616171@qq.com。
基金资助:
国家自然科学基金面上项目（81271501）；国家临床重点专科建设项目[财社（2011）170号]；重庆市应用开发计划项目（cstc2014yykfA110028）；重庆市医学重点学科建设项目[渝卫科教（2007）2号]；重庆市基础与前沿研究计划（cstc2016jcyjA0100）；重庆医科大学附属永川医院院内科研课题（YJJC201905）

Role of group Ⅰ mGluR in low dose ketamine protecting learning and memory function after electroconvulsive shock in depression rats

LIU Da-wei1, REN Li2, MIN Su2

1. Department of Anesthesiology, Yongchuan Hospital of Chongqing Medical University, Chongqing 402160, China; 2. Department of Anesthesiology, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China

Online:2019-11-28 Published:2019-12-16
Supported by:
National Natural Science Foundation of China，81271501; National Clinical Key Specialist Construction Project, Caishe (2011) No. 170; Chongqing Application Development Plan Project, cstc2014yykfA110028; Chongqing Medical Key Discipline Construction Project, Yuwei Science Education (2007) No. 2; Chongqing Basic and Frontier Research Program, cstc2016jcyjA0100; In-hoScientific Research Project of the Yongchuan Hospital of Chongqing Medical University, YJJC201905

摘要/Abstract

摘要： 目的·探讨Ⅰ型促代谢性谷氨酸受体（groupⅠ metabotropic glutamate receptor， Ⅰ型mGluR）调节谷氨酸N-甲基-D-天冬氨酸受体（N-methyl-D-aspartic acid receptor，NMDAR）介导的突触可塑性在小剂量氯胺酮保护抑郁大鼠改良电休克（modified electroconvulsive shock，MECS）后空间学习记忆功能中的作用。方法·对2～3月龄Sprague Dawley（SD）大鼠，应用慢性不可预见性应激建立抑郁模型。取10只健康大鼠作为对照组（C组），另取30只抑郁大鼠随机分为D组、M组、KM组。C组不予实验处理；D组腹腔注射生理盐水后行伪MECS处理；M组腹腔注射丙泊酚，KM组腹腔注射丙泊酚复合小剂量氯胺酮（10 mg/kg），之后分别行MECS处理。应用糖水偏好实验评估抑郁状态；Morris水迷宫检测空间学习记忆功能； Western blotting检测海马组织细胞膜NMDAR1、mGluR1、mGluR5蛋白表达。另取36只抑郁大鼠随机分为6组：DE组、m1E组、m5E组，DE组、m1E组、m5E组。DE组、DE组脑片灌流单纯人工脑脊液；m1E组、m1E组脑片灌流含有mGluR1阻断剂的人工脑脊液；m5E组、m5E组脑片灌流含有mGluR5阻断剂的人工脑脊液。检测DE组、m1E组、m5E组长时程增强（long-term potentiation，LTP）以及DE组、m1E组、m5E组NMDAR介导的场电位（fEPSPNMDAR）。结果·实验处理后，与D组比较，M组和KM组糖水偏好百分比升高（PPPPPPPP组比较，m1E组和m5E组fEPSPNMDAR降低（P结论·小剂量氯胺酮可能通过上调抑郁大鼠MECS后海马组织细胞膜NMDAR和Ⅰ型mGluR表达，增强NMDAR激活状态同时上调LTP，减轻空间学习记忆功能损伤。

关键词: 氯胺酮, 电休克, 学习记忆功能, Ⅰ型促代谢性谷氨酸受体, 突触可塑性, 大鼠

Abstract:

Objective · To investigate the role of group I metabotropic glutamate receptor (mGluR) in the regulation of N-methyl-D-aspartic acid receptor (NMDAR)-mediated synaptic plasticity in low dose ketamine protecting learning and memory function after modified electroconvulsive shock (MECS). Methods · The 2-3-month-old Sprague Dawley (SD) rats were used to establish depression models with chronic unpredicmild stress. Ten healthy rats were used as the control group (group C), and another 30 depressed rats were randomly divided into group D, group M, and group KM. Group C was not treated, group D was treated with pseudo-MECS after intraperitoneal injection of normal saline, group M was given intraperitoneal injection of propofol, and group KM was given intraperitoneal injection of propofol combined with low-dose ketamine (10 mg/kg). Both group M and group KM underwent MECS. The sucrose preference test was used to evaluate the depression status. The Morris water maze was used to detect the spatial learning and memory function. The of NMDAR1, mGluR1 and mGluR5 proteins in the hippocampus was detectedWestern blotting. Another 36 depressed rats were randomly divided into 6 groups: group DE, group m1E, group m5E, group DE, group m1E, and group m5E. Group DE and group DE were perfused with artificial cerebrospinal fluid alone. Group m1E and group m1E were perfused with artificial cerebrospinal fluid containing mGluR1 blocker. Group m5E and group m5E were perfused with artificial cerebrospinal fluid containing mGluR5 blocker. Long-term potentiations (LTP) were detected in group DE, group m1E, and group m5E. NMDAR-mediated field potentials (fEPSPNMDAR) were detected in group DE, group m1E, and group m5E. Results · After treatment, the sucrose preference percentages of group M and group KM increased compared with group D (PPPPPPPPNMDAR of group m1E and group m5E decreased (PConclusion · Ketamine up-regulates NMDAR1 and group ⅠmGluR to enhance the activation of NMDAR in the hippocampus which may be responsible for the protective effects on spatial learning and memory function in depression rats undergoing MECS.

Key words: ketamine, electroconvulsive shock, learning and memory function, group Ⅰ metabotropic glutamate receptor, synaptic plasticity, rat

中图分类号:

R749.054

刘大为1，任力2，闵苏2. Ⅰ型促代谢性谷氨酸受体在小剂量氯胺酮保护抑郁大鼠电休克后学习记忆功能中的作用[J]. 上海交通大学学报（医学版）, 2019, 39(11): 1248-.

LIU Da-wei1, REN Li2, MIN Su2. Role of group Ⅰ mGluR in low dose ketamine protecting learning and memory function after electroconvulsive shock in depression rats[J]. , 2019, 39(11): 1248-.

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Ⅰ型促代谢性谷氨酸受体在小剂量氯胺酮保护抑郁大鼠电休克后学习记忆功能中的作用

Role of group Ⅰ mGluR in low dose ketamine protecting learning and memory function after electroconvulsive shock in depression rats

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