异氟烷对神经认知功能的影响及其可能机制  

Effects of Isoflurane On Neurocognitive Function and Its Possible Mechanism

作　　者：吴倍 王新生[2] 杨跃平[1] 滕金亮[2] WU Bei WANG Xin-sheng YANG Yue-ping TENG Jin-liang(Hebei North University, Zhangjiakou, 075000, China The First Affiliated Hospital of Hebei North University, Zhangjiakou, 075000, China)

机构地区：[1]河北北方学院 [2]河北北方学院附属第一医院

出　　处：《神经药理学报》2015年第5期34-39,共6页Acta Neuropharmacologica

基　　金：河北北方学院自然科学研究计划项目(No.120176);2016年政府资助省级临床医学优秀人才项目

摘　　要：大量实验证据表明异氟烷能够引起学习和认知能力改变。这可能是其抑制N-甲基-D-天冬氨酸(N-methyl-D-aspartic acid,NMDA)受体、激活γ-氨基丁酸(γ-amino butyric acid,GABA)受体引起神经细胞去极化、Ca^(2+)内流,促使激活caspase-3,造成神经元毒性。异氟烷也能够改变突触的形成及树突棘的密度,引起发育期的神经元死亡,造成行为学改变。它过度激活钙调蛋白,抑制海马区突触长时程电位(long term potentiation,LTP),抑制短期记忆向长期记忆的转换。异氟烷引起蛋白激酶R样内质网激酶(PRKR-like endoplasmic reticulum kinase,PERK)磷酸化,通过一系列分子机制,诱导转录因子C/EBP同源蛋白(C/EBP homologous protein,CHOP)的表达,CHOP上调促凋亡蛋白和下调抗凋亡蛋白来促进神经元凋亡。此外,异氟烷诱导tau蛋白的高度磷酸化,形成神经纤维结,神经纤维结的形成被认为是神经失能性疾病比如阿尔茨海默病的共同病理途径。该文重点就异氟烷对神经认知的影响及其机制进行综述。A lot of experimental evidences showed that isoflurane can cause the change of learning and cognitive ability,resulting from the inhibition of N-methyl-D-aspartic acid（NMDA）receptor,depolarization induced by activation of gamma aminobutyric acid（GABA） receptor,Ca^（2＋）influx and promote activation of caspase-3 which leads to neuronal toxicity.Volatile anesthetics could interfere with physiologic patterns of synaptogenesis and impair density of endritic spines of neurons in the developing cerebral cortex,thus causing changes in behavior.Isoflurane excessively activates calmodulin,inhibits hippocampal synaptic long term potential（LTP） and curbs short-term memory into long-term memory conversion.Isoflurane induces PERK phosphorylation and increases the expression of CHOP by a series of molecular mechanisms.CHOP up-regulates pro-apoptotic proteins and downregulates anti-apoptotic proteins to promote neuronal apoptosis.Tau protein is highly phosphorylated in the form of nerve fibers and the formation of nerve fibers is considered as a common pathological pathway in the pathogenesis of Alzheimer＇ s disease.In this review,the mechanism of the general anesthetics inducing consciousness loss and its effect of central nervous system were summarized.

关 键 词：异氟烷 术后认知障碍 内质网应激 钙调蛋白 

分 类 号：R741[医药卫生—神经病学与精神病学] R964[医药卫生—临床医学]