Ⅱ组代谢型谷氨酸受体在多次给予氯胺酮致小鼠认知功能降低中的作用:与海马GSK3β表达的关系  

Role of groupⅡmetabotropic glutamate receptors in cognitive decline caused by multiple administrations of ketamine in mice:the relationship with hippocampal GSK3βexpression

作　　者：黄梦婷 温博伦 庹鹏 陈伟明[1] 陈晓彤[2] 詹鸿[1] 王寿平[1] Huang Mengting;Wen Bolun;Tuo Peng;Chen Weiming;Chen Xiaotong;Zhan Hong;Wang Shouping(Department of Anesthesiology,Third Affiliated Hospital of Guangzhou Medical University,Guangzhou 510150,China;Department of Anesthesiology,Sun Yat-sen Memorial Hospital,Sun Yat-sen University,Guangzhou 510120,China)

机构地区：[1]广州医科大学附属第三医院麻醉科,510150 [2]中山大学孙逸仙纪念医院博济医疗中心麻醉科,广州510120

出　　处：《中华麻醉学杂志》2019年第5期544-547,共4页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金(81271223);广东省自然科学基金(S2012010009065,2014A030313112);广州市科技计划项目(201707010379)

摘　　要：目的评价Ⅱ组代谢型谷氨酸受体在多次给予氯胺酮致小鼠认知功能降低中的作用及其与海马糖原合成酶激酶3β(GSK3β)表达的关系。方法SPF级健康雌性C57BL/6小鼠45只,6~8周龄,体重20~30 g,采用随机数字表法分为3组(n=15):对照组(C组)、氯胺酮组(K组)和Ⅱ组代谢型谷氨酸受体激动剂组(L+K组)。K组和L+K组腹腔注射氯胺酮30 mg/kg,间隔30 min注射1次,3次/d,连续14 d;L+K组于第1次注射氯胺酮前30 min腹腔注射Ⅱ组代谢型谷氨酸受体激动剂LY354740 10 mg/kg;C组给予生理盐水。末次给药次日行Morris水迷宫实验,随后处死小鼠取海马,采用Western blot法测定GSK3β、NR2A和突触后致密蛋白95(PSD95)的表达。结果与C组比较,K组逃避潜伏期延长,原平台象限停留时间缩短,原平台穿越次数减少,海马GSK3β和NR2A表达上调,PSD95表达下调(P<0.05),L+K组上述指标差异无统计学意义(P>0.05);与K组比较,L+K组逃避潜伏期缩短,原平台停留时间延长,原平台穿越次数增多,海马GSK3β和NR2A表达下调,PSD95表达上调(P<0.05)。结论Ⅱ组代谢型谷氨酸受体参与了多次给予氯胺酮致小鼠认知功能降低的过程,与海马GSK3β表达上调有关。Objective To evaluate the role of groupⅡmetabotropic glutamate receptors(mGluRs)in cognitive decline caused by multiple administrations of ketamine in mice and the relationship with hippocampal glycogen synthase kinase-3 beta(GSK-3β)expression.Methods Forty-five SPF healthy female C57BL/6 mice,aged 6-8 weeks,weighing 20-30 g,were randomized into 3 groups(n=15 each)using a random number table method:control group(group C),ketamine group(group K)and mGluR agonist LY354740 group(group L+K).In K and L+K groups,ketamine 30 mg/kg was intraperitoneally injected three times a day at an 30-min interval for 14 consecutive days.LY354740 was intraperitoneally injected at 30 min before the first injection of ketamine in group L+K.The equal volume of normal saline was given instead in group C.Morris water maze test was performed the day after the last administration.The mice were then sacrificed,and hippocampi were harvested to determine the expression of GSK3β,NR2A and postsynaptic density protein 95(PSD95)by Western blot.Results Compared with group C,the escape latency was significantly prolonged,the time of staying at the original platform quadrant was shortened,the frequency of crossing the original platform was decreased,the expression of GSK3βand NR2A was up-regulated,and the expression of PSD95 was down-regulated in group K(P<0.05),and no significant change was found in the parameters mentioned above in group L+K(P>0.05).Compared with group K,the escape latency was significantly shortened,the time of staying at the original platform quadrant was prolonged,the frequency of crossing the original platform was increased,the expression of GSK3βand NR2A was down-regulated,and the expression of PSD95 was up-regulated in group L+K(P<0.05).Conclusion GroupⅡmGluRs are involved in the process of cognitive decline caused by multiple administrations of ketamine in mice,which is associated with up-regulated expression of hippocampal GSK-3β.

关 键 词：受体 谷氨酸 氯胺酮 认知障碍 糖原合成酶激酶3Β 

分 类 号：R61[医药卫生—外科学]