氯胺酮与七氟醚诱导老龄小鼠POCD的病理机制比较  

Comparison of pathological mechanisms of POCD induced by ketamine or sevoflurane in aged mice

作　　者：黄钰媛 韦雪梅 郑育秀 刘丽丽[1] HUANG Yuyuan;WEI Xuemei;ZHENG Yuxiu;LIU Lili(Department of Anesthesiology,The Second Affiliated Hospital of Hainan Medical College,Haikou 570311,China)

机构地区：[1]海南医学院第二附属医院麻醉科,海南海口570311

出　　处：《西部医学》2022年第5期658-664,共7页Medical Journal of West China

基　　金：海南省基础与应用基础研究计划项目(818QN319)。

摘　　要：目的比较氯胺酮与七氟醚诱导老龄小鼠POCD的病理变化,并探讨其机制。方法将36只12月龄C57BL/6小鼠,随机分为对照组,氯胺酮组与七氟醚组,以200 mg/kg的氯胺酮和3%七氟醚麻醉小鼠,维持6 h。麻醉前后以Morris水迷宫检测学习与记忆能力。取小鼠脑组织,采用长时程电位测试记录海马区兴奋性突触后电位,通过高尔基染色检测海马区神经元突触状态,利用免疫组化染色观察脑组织中Aβ沉积,最后以Western blot检测小鼠脑组织中NMDA受体与凋亡蛋白表达。结果与对照组相比,在游泳速率没有改变的情况下,氯胺酮与七氟醚都造成了小鼠逃避潜伏期增加,穿越平台次数减少,第Ⅰ象限停留时间增加。氯胺酮组小鼠Morris水迷宫各项指标优于七氟醚组。病理检测显示,虽然氯胺酮与七氟醚都造成了小鼠LTP抑制,突触中树突棘密度和长度减少,Aβ沉积增加,但七氟醚组小鼠海马区LTP水平与树突棘状态明显劣于氯胺酮组,且Aβ沉积增加。氯胺酮与七氟醚都明显抑制了NMDAR表达,且Caspase-3信号通路被明显激活。氯胺酮对NMDAR抑制作用明显高于七氟醚,且相比于七氟醚组,氯胺酮组小鼠bcl-2表达更高。结论相比于七氟醚,氯胺酮对老龄小鼠认知功能的影响较小,其生理机制涉及NMDAR受体的抑制,部分抑制了Aβ沉积,升高了LTP水平。Objective To compare the pathological changes of POCD induced by ketamine and sevoflurane in aged mice,and explore its possible mechanism.Methods 12-month-old C57BL/6 mice were randomly divided into Control group,Ketamine group and Sevoflurane group.The mice were anesthetized with a total dose of 200 mg/kg of ketamine and 3% sevoflurane for 6 hours.Morris water maze was used to test the learning and memory ability.Then,excitatory postsynaptic potential was detected by long-term potential test,synaptic state was detected by Golgi staining,Aβ deposition in brain was observed by immunohistochemical staining,and the expression of NMDAR and apoptosis protein in brain were detected by Western blot.Results Compared with Control group,no matter ketamine or sevoflurane caused significant increases of escape latency,a decrease of platform crossing number,and an increase of resident time in the first quadrant at the same swimming speed.However,all indexes of Morris water maze mice in Ketamine group were better than those in Sevoflurane group.In addition,both ketamine and sevoflurane caused LTP inhibition in mice,reduced the density and length of dendritic spines in synapses,and increased Aβ deposition.However,compared with Ketamine group,mice in Sevoflurane group had lower LTP intensity,decreased dendritic spines density,and increased Aβ deposition.In addition,Western blot showed that both ketamine and sevoflurane significantly inhibited the expression of NMDAR,and the Caspase-3 signaling pathway was significantly activated.The inhibition of ketamine on NMDAR was better than sevoflurane,and the expression of bcl-2 was higher in mice of Ketamine group than Sevoflurane group.Conclusion Compared with Sevoflurane group,Ketamine has less effects on cognitive function in aged mice,which involving the inhibition of NMDAR receptors,mediates the decrease of Aβ deposition and the increase of LTP level.

关 键 词：氯胺酮 七氟醚 老龄小鼠 术后认知功能障碍 β-淀粉样蛋白沉积 

分 类 号：R614[医药卫生—麻醉学]