小剂量氯胺酮减轻老龄大鼠七氟醚麻醉后认知功能障碍的机制:GluR2/N-cadherin信号通路介导的内嗅皮质突触可塑性  

Mechanism of small-dose ketamine in reducing cognitive impairment after sevoflurane anesthesia in aged rats: synaptic plasticity mediated by GluR2/N-cadherin signaling pathway in entorhinal cortex

作　　者：魏伟[1] 李传翔 陈雁信 卢俊鸣 赵天云[1] 宋兴荣[1] Wei Wei;Li Chuanxiang;Chen Yanxin;Lu Junming;Zhao Tianyun;Song Xingrong(Department of Anesthesiology,Guangzhou Women and Children′s Medical Center,Guangzhou Medical University,Guangzhou 510623,China;Department of Anesthesiology,the Third Affiliated Hospital of Southern Medical University,Guangzhou 510515,China)

机构地区：[1]广州医科大学附属广州市妇女儿童医疗中心麻醉科,510623 [2]南方医科大学第三附属医院麻醉科,广州510515

出　　处：《中华麻醉学杂志》2019年第12期1433-1436,共4页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金面上项目(81671116);广东省自然科学基金(2016A030313635);广州市科技计划项目(201707010039,201803010025)。

摘　　要：目的评价含Glu2亚基的AMPA受体(GluR2)/N-钙黏蛋白(N-cadherin)信号通路介导的内嗅皮质突触可塑性与小剂量氯胺酮减轻老龄大鼠七氟醚麻醉后认知功能障碍的关系。方法清洁级健康雄性SD大鼠27只,18月龄,体重500~600 g,采用随机数字表法分为3组(n=9):对照组(C组)、七氟醚麻醉组(Sev组)和氯胺酮组(K组)。Sev组和K组吸入3.6%七氟醚和1 L/min空气的混合气体3 h;K组麻醉前5 min时腹腔注射氯胺酮10 mg/kg。麻醉后3 d时行旷场实验和Morris水迷宫实验。行为学测试结束后处死大鼠,测定内嗅皮质Ⅱ-Ⅲ层突触密度和兴奋性突触百分比,采用Western blot法检测内嗅皮质GluR2、β-catenin和N-cadherin的表达水平。结果与C组比较,Sev组中央区停留时间缩短,逃避潜伏期延长,内嗅皮质Ⅱ-Ⅲ层突触密度和兴奋性突触百分比下降,内嗅皮质GluR2、β-catenin和N-cadherin表达下调(P<0.05),K组上述指标差异无统计学意义(P>0.05);与Sev组比较,K组中央区停留时间延长,逃避潜伏期缩短,内嗅皮质Ⅱ-Ⅲ层突触密度和兴奋性突触百分比升高,内嗅皮质GluR2、β-catenin和N-cadherin表达上调(P<0.05)。结论小剂量氯胺酮减轻老龄大鼠七氟醚麻醉后认知功能障碍的机制可能与激活GluR2/N-cadherin信号通路,增强内嗅皮质突触可塑性有关。Objective To evaluate the relationship between synaptic plasticity mediated by Glu2 subunit-containing AMPA receptors(GluR2)/N-cadherin signaling pathway in the entorhinal cortex and small-dose ketamine-induced reduction of cognitive impairment after sevoflurane anesthesia in aged rats.Methods Twenty-seven clean-grade healthy male Sprague-Dawley rats,aged 18 months,weighing 500-600 g,were divided into 3 groups(n=9 each)using a random number table method:control group(group C),sevoflurane group(group Sev)and ketamine group(group K).Rats were exposed to 3.6%sevoflurane in 1 L/min air for 3 h in Sev and K groups.Ketamine 10 mg/kg was intraperitoneally injected at 5 min before anesthesia.The behavioral tests including open-field test and Morris water maze test were conducted to assess the cognitive function at 3 days after anesthesia.Rats were sacrificed after behavioral testing to detect the density of synapses and the percentage of the excitatory synapses and to determine the expression of GluR2,β-catenin and N-cadherin in the entorhinal cortex(by Western blot assay).Results Compared with C group,the time of staying at the central region was significantly shortened,the escape latency was prolonged,the synapse density and percentage of excitatory synapses in the entorhinal cortex laminaⅡ-Ⅲwere decreased,and the expression of GluR2,β-catenin and N-cadherin was down-regulated in Sev group(P<0.05),and no significant change was found in the parameters mentioned above in K group(P>0.05).Compared with Sev group,the time of staying at the central region was significantly prolonged,the escape latency was shortened,the synapse density and percentage of excitatory synapses in entorhinal cortex laminaⅡ-Ⅲwere increased,and the expression of GluR2,β-catenin and N-cadherin was up-regulated in K group(P<0.05).Conclusion The mechanism by which small-dose ketamine reduces cognitive dysfunction caused by sevoflurane anesthesia may be related to activating GluR2/N-cadherin signaling pathway and enhancing synaptic plasticity

关 键 词：氯胺酮 麻醉药 吸入 认知功能障碍 老年人 受体 AMPA 钙黏着糖蛋白类 内嗅皮层 神经元可塑性 

分 类 号：R614[医药卫生—麻醉学]