[1]陈晓梅,卢晨昕.右美托咪啶预处理对改善谷氨酸诱导神经元活化与小鼠焦虑样行为的研究[J].福建医药杂志,2022,44(01):114-117.
　CHEN Xiaomei,LU Chenxin.Effect of dexmedetomidine premedication on neuronal activation and anxiety-like behavior induced by glutamine in mice[J].FUJIAN MEDICAL JOURNAL,2022,44(01):114-117.
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右美托咪啶预处理对改善谷氨酸诱导神经元活化与小鼠焦虑样行为的研究()
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《福建医药杂志》[ISSN:1002-2600/CN:35-1071/R]

卷:
44
期数:
2022年01期
页码:
114-117
栏目:
基础研究
出版日期:
2022-02-15

文章信息/Info

Title:
Effect of dexmedetomidine premedication on neuronal activation and anxiety-like behavior induced by glutamine in mice
文章编号:
1002-2600(2022)01-0114-04
作者:
陈晓梅; 卢晨昕
厦门大学附属福州第二医院麻醉科(福州350007)
Author(s):
CHEN Xiaomei;  LU Chenxin
Department of Anesthesiology, the Affiliated Fuzhou Municipal Second Hospital of Xiamen University, Fuzhou, Fujian 350007, China
关键词:
焦虑障碍; 谷氨酸; 右美托咪啶
Keywords:
anxiety-like behavior;  glutamine;  dexmedetomidine
分类号:
R614
文献标志码:
B
摘要:
目的 评价右美托咪啶预先处理改善谷氨酸诱导HT22神经元活化与小鼠焦虑样行为。方法 体外培养HT22神经元，予0、0.5、1、5、10、20mM L-谷氨酸孵育3、6、12、24h，采用Calcein AM染色检测细胞活率;予0.05和0.1μg/mL右美托咪啶(Dex)、AMPA受体拮抗剂(DNXQ)、抗组胺剂哌罗克生(Piperoxan)预先处理HT22细胞后，采用1mM和5mM L-谷氨酸孵育12h,检测乳酸脱氢酶(LDH)释放和活性氧(ROS) 产生。基底外侧杏仁核内立体定位注射L-谷氨酸诱导小鼠抑郁样行为，予1μL (50μg/mL)、1μL (100μg/mL) Dex、DNXQ、Piperoxan预先处理，采用旷场和高架十字迷宫实验检测小鼠焦虑样行为。结果 L-谷氨酸处理HT22细胞呈浓度和时间依赖性诱导细胞死亡;与CONT 组相比，Glu组细胞内游离Ca2+含量、LDH释放率和ROS+HT22比例显著增高(P<0.05)，且可被DNQX和Dex逆转(P<0.05);与Glu+Dex组相比，Piperoxan预先处理可逆转Dex对HT22的保护作用(P<0.05)。与CONT组相比，Glu组旷场中央区域活动时间百分比、高架十字迷宫开臂停留时间百分比和开臂进人次数百分比显著降低(P<0.05)，且可被DNQX和Dex逆转(P<0.05);与Glu+Dex组相比，Piperoxan预先处理可逆转Dex的抗焦虑作用(P<0.05)。 结论 Dex通过激活α2-肾上腺素受体，抑制谷氨酸诱导的胞内钙离子浓度升高、神经元过度活化和氧化应激，并有效改善小鼠焦虑样行为的产生。
Abstract:
Objective To evaluate the effect of dexmedetomidine (Dex) premedication on HT22 activation and anxiety-like behavior induced by glutamine in mice. Methods HT22 cells were culture in vitro and incubated with0, 0.5, 1, 5，10, and 20 mM L-glutamine for 3，6，12，24 h. Calcein AM staining was applied to evaluate the cellular survival. Moreover, 0.05 and 0.1 μg/mL Dex, DNXQ, and Piperoxan were premedication for 60 min respectively, and 1 and 5 mM L-glutamine was applied to incubate for another 12 h, thereafter, and then LDH release and ROS production were detected. Mice were stereotactically injected with L-glutamine in the basolateral nucleus of amygdale to induce anxiety-like behavior. Premedication with 1 μL (50 μg/mL)、1 μL (100 μg/mL) Dex, DNXQ, and Piperoxan were performed, and open field and elevated plus maze test were applied to evaluate the protective effect on reversing anxiety like behavior. Results L glutamine induced HT22 cell death in a dose- and time-dependent manner. Compared with CONT group, intracellular calcium concentration， LDH release, and ROS production were significantly increased (P<0.05)，but reversed by Dex and DNQX premedication (P<0.05). Compared with Glu+Dex group, Piperoxan premedication reversed the protective effect of Dex on HT22 (P<0.05). Compared with CONT group, mice in Glu group presented decreased the percentage of time spent in the central zone in the open field test, as well as the percentage of time spent in the open arms and entries in the open arms in the elevated plus maze test (P<0.05)，but reversed by Dex and DNQX premedication (P<0.05). Compared with Glu+Dex group, Piperoxan premedication reversed the anti-anxiety effect of Dex in mice (P<0.05). Conclusion Dex can inhibit glutamine-induced increase of intracellular calcium concentration, neuronal over-activation, oxidative stress in HT22 cell, and can improve anxiety-like behavior in mice via activation of α2-adrenergic receptor.

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备注/Memo

备注/Memo:
基金项目: 2016年福建省医学创新课题B类(2016CXB-5)
更新日期/Last Update: 2022-02-15