文献类型：期刊文献

中文题名：美金刚对小鼠七氟烷麻醉深度和围术期认知功能的影响

英文题名：Effects of memantine on sevoflurane anesthetic depth and perioperative neurocognitive disorders in mice

作者：蒋尚[1];傅巍[1];李玉兰[2,1];马礼科[3];康万荣[4];马雪[1];臧宏刚[5]

第一作者：蒋尚

机构：[1]兰州大学第一临床医学院,甘肃兰州730000;[2]兰州大学第一医院麻醉手术科,甘肃兰州730000;[3]甘肃中医药大学第一临床医学院,甘肃兰州730000;[4]甘肃中医药大学科研实验中心,甘肃兰州730000;[5]甘肃省人民医院麻醉手术科,甘肃兰州730000

第一机构：兰州大学第一临床医学院,甘肃兰州730000

年份：2025

卷号：41

期号：6

起止页码：1118

中文期刊名：中国病理生理杂志

外文期刊名：Chinese Journal of Pathophysiology

收录：;北大核心:【北大核心2023】；

基金：甘肃省青年科技基金资助项目(No.21JR11RA202)。

语种：中文

中文关键词：围术期神经认知障碍;七氟烷;美金刚;爆发抑制比

外文关键词：perioperative neurocognitive disorders;sevoflurane;memantine;burst suppression ratio

摘要：目的:探究N-甲基-D-天冬氨酸(NMDA)受体拮抗剂美金刚(Mem)干预对小鼠七氟烷(Sev)麻醉深度及围术期神经认知障碍的影响,并探讨其发挥作用的可能机制。方法:构建小鼠脑电图(EEG)监测模型和认知障碍模型。(1)EEG监测部分:将雄性C57BL/6J小鼠随机分为对照(control)组、Sev组和Mem+Sev组。麻醉前7 d小鼠头部植入脑电监测电极,麻醉当日Mem+Sev组腹腔注射20 mg/kg溶于生理盐水的Mem;control组和Sev组小鼠按体重腹腔注射等体积生理盐水,30 min后Sev组和Mem+Sev组采用400 mL/min O2+3%Sev麻醉5 h,control组采用400 mL/min O2处理5 h;待Sev组和Mem+Sev组小鼠翻正反射恢复后结束3组EEG监测,记录小鼠翻正反射消失和恢复时间,分析小鼠EEG爆发抑制比及各波段相对功率变化。(2)Sev麻醉后认知障碍部分:另选同一批次雄性C57BL/6J小鼠,分组同前,麻醉前6 d进行水迷宫定位航行训练。麻醉当日,Mem+Sev组腹腔注射20 mg/kg溶于生理盐水的Mem,control组和Sev组小鼠按体重腹腔注射等体积生理盐水,30 min后Sev组和Mem+Sev组采用400 mL/min O2+3%Sev麻醉5 h,control组采用400 mL/min O2处理5 h;麻醉后3 d进行定位航行测试和空间探索测试。测试结束后,处死小鼠取材海马组织。ELISA法检测海马组织白细胞介素1β(IL-1β)、肿瘤坏死因子α(TNF-α)和乙酰胆碱(ACh)水平;钙试剂盒检测海马组织Ca2+浓度;HE染色观察海马CA3区病理变化;Western blot法检测NMDA受体GluN1亚基、γ-氨基丁酸A型受体、β-淀粉样蛋白(Aβ)和磷酸化tau蛋白(p-tau)水平。结果:与control组相比,Sev组麻醉期间各时间段爆发抑制比均升高,麻醉3 d后逃避潜伏时间延长、穿越平台次数减少(P<0.05);海马组织IL-1β和TNF-α含量增加,ACh含量降低,Ca2+浓度增加,GluN1亚基、Aβ和p-tau蛋白表达升高(P<0.05);与Sev组相比,Mem+Sev组麻醉诱导时间缩短,麻醉期间各时间段爆发抑制比均升高,慢波和δ波相对功率升高(P<0.05);麻醉3 d后逃避潜伏期时间缩短、穿越平台次数增加(P<0.05);海马组织IL-1β、TNF-α和ACh含量增加,GluN1亚基、Aβ和p-tau蛋白表达降低(P<0.05);麻醉苏醒时间的差异无统计学意义(P>0.05)。结论:Mem协同Sev麻醉,加快麻醉诱导,加深Sev麻醉深度,这可能与其增强δ脑电波相对功率有关,但对苏醒时间无明显影响;Mem干预抑制NMDA受体、Aβ和p-tau蛋白过度表达,并减轻神经炎症,从而缓解Sev麻醉所致认知障碍。
AIM:To investigate the effects of memantine(Mem),an N-methyl-D-aspartate(NMDA)receptor antagonist,on sevoflurane(Sev)anesthetic depth and perioperative neurocognitive disorders in mice,and to explore the possible mechanisms involved.METHODS:Mouse electroencephalogram(EEG)monitoring and cognitive disorder models were established.For EEG monitoring,male C57BL/6J mice were randomly divided into control group,Sev group,and Mem+Sev group.The EEG monitoring electrodes were implanted in the heads of the mice 7 d before anesthesia.On the day of anesthesia,the mice in Mem+Sev group received an intraperitoneal injection of 20 mg/kg Mem dissolved in normal saline,while those in control and Sev groups received intraperitoneal injection of an equivalent volume of normal saline based on body weight.Thirty minutes later,the mice in Sev and Mem+Sev groups were anesthetized with 400 mL/min O2+3%Sev for 5 h,while those in control group were treated with 400 mL/min O2 for 5 h.The EEG monitoring was terminated after the righting reflex was restored in Sev and Mem+Sev groups.The time of disappearance and recovery of the righting reflex was recorded,and changes in EEG burst suppression ratio and relative power of each frequency band were analyzed.For the cognitive disorder part,another batch of male C57BL/6J mice were selected and divided into the same groups as before.The mice underwent water maze spatial navigation training for 6 d before anesthesia.On the day of anesthesia,the mice in Mem+Sev group received an intraperitoneal injection of 20 mg/kg Mem dissolved in normal saline,while those in control and Sev groups received intraperitoneal injection of an equivalent volume of normal saline based on body weight.Thirty minutes later,the mice in Sev and Mem+Sev groups were anesthetized with 400 mL/min O2+3%Sev for 5 h,and those in control group were treated with 400 mL/min O2 for 5 h.Spatial navigation and exploration tests were conducted 3 d after anesthesia.After the tests,the mice were sacrificed,and their hippocampal tissues were collected.The levels of interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α)and acetylcholine(ACh)in the hippocampal tissues were detected by ELISA.The concentration of Ca2+in the hippocampal tissues was measured using a calcium assay kit.Pathological changes in the hippocampal CA3 region were observed by HE staining,and the protein levels of NMDA receptor GluN1 subunit,GABAA receptor,amyloidβ-protein(Aβ),and p-tau were detected by Western blot.RESULTS:Compared with control group,the mice in Sev group had increased burst suppression ratio at all time points during anesthesia and prolonged escape latency and reduced platform crossings 3 d after anesthesia(P<0.05).The levels of IL-1βand TNF-αin the hippocampal tissues increased,while the level of ACh decreased,and the concentration of Ca2+increased.The protein levels of GluN1 subunit,Aβand p-tau were elevated(P<0.05).Compared with Sev group,the mice in Mem+Sev group had shortened anesthesia induction time and increased burst suppression ratio at all time points during anesthesia,with elevated relative power of slow waves andδwaves(P<0.05).The escape latency was shortened,and the platform crossings increased 3 d after anesthesia(P<0.05).The levels of IL-1βand TNF-αin the hippocampal tissues decreased,while the levels of ACh increased,and the protein levels of GluN1 subunit,Aβand p-tau were reduced(P<0.05).There was no significant difference in anesthesia recovery time among the groups(P>0.05).CONCLUSION:Memantine,in combination with Sev anesthesia,accelerates anesthesia induction and deepens anesthetic depth,which may be related to the increased relative power ofδEEG waves,but has no significant effect on recovery time.Memantine intervention alleviates Sev anesthesia-induced cognitive disorders by inhibiting the overexpression of NMDA receptors,Aβand p-tau,and attenuating neuroinflammation.