七氟烷通过激活GluN2B－ERK1／2信号通路抑制ADDLs神经毒性  

Sevoflurane inh ibits ADDL neurotoxicity via activation the GluN2B -ERK1/2 signaling pathway

作　　者：郝景茹[1] 胡蕊[1] 胡秋梅[1] 高灿[1] 

机构地区：[1]徐州医学院江苏省麻醉学重点实验室,江苏徐州221004

出　　处：《徐州医学院学报》2015年第8期491-496,共6页Acta Academiae Medicinae Xuzhou

基　　金：国家自然科学基金（81273489,81471101）;江苏省高校自然科学研究重大项目（12KJA180008）;江苏省自然科学基金（BK2012582）;江苏高校青蓝工程科技创新团队项目

摘　　要：目的：探讨七氟烷对Aβ来源的扩散性配体（Aβ－derived diffusible ligands，ADDLs）神经毒性的影响，揭示七氟烷对阿尔茨海默病（Alzheimer disease， AD）损伤神经元的保护作用及其机制。方法体外培养2周的大鼠海马神经元随机分为4组：对照组、ADDLs 组、七氟烷组以及合用组。免疫印迹方法观察七氟烷及ADDLs对p －ERK1／2、NMDA受体各亚基表达、GluN2B 亚基的第172位酪氨酸磷酸化水平的影响；细胞组分分离方法探索七氟烷及 ADDLs 影响NMDA受体各亚基在细胞膜表面表达的规律；细胞免疫荧光化学方法检测七氟烷及AD－DLs对GluN2B 亚基在突触上表达水平的影响。结果1．5％七氟烷作用2h可显著恢复ADDLs降低的ERK1／2的活化水平；1．5％七氟烷处理2 h可显著逆转ADDLs降低的GluN1和GluN2B亚基在细胞膜表面表达的水平，但是对细胞膜表面 GluN2A的表达水平无明显影响，对NMDA受体各亚基总的表达水平无影响；细胞免疫荧光化学结果显示七氟烷可以显著增加ADDLs降低的GluN2B亚基在突触上的表达量。结论七氟烷通过激活GluN2B－ERK1／2信号通路抑制ADDLs的神经毒性。Objective To investigate the effects of sevoflurane on ADDL neurotoxicity and explore the protective mechanism by which sevoflurane protects neurons against Alzheimer disease （AD）.Methods After cultivation for two weeks, rat primary hippocampal neurons were divided into four groups, namely a control group, an ADDL group, a sevoflurane group and a combination group.Then, the amounts of p -ERK1 /2,the subunits of NMDA receptor, and p -GluN2B subunits Tyr1472 were detected by immunoblotting after treatment of sevoflurane and/or ADDLs.Subcellular fractions of the cells were extracted to explore the effects of sevoflurane and ADDLs on the levels of NMDA receptor sub-units on the surface of cellular membrane.The effects of sevoflurane and ADDLs on GluN2B subunits distribution on the synapse were examined by immunofluorescence.Results After treatment for 2 h, 1.5% sevoflurane could remarkably reverse the level of p -ERK1/2, as well as the amounts of GluN1 and GluN2B on the surface of cellular membrane in-duced by ADDLs.However, such treatment did not affect the expression of GluN2A and the subunits of NMDA receptor in total.Sevoflurane also substantially enhanced the reduced level of GluN 2B subunit on the synapse by ADDLs.Conclu-sion Sevoflurane can inhibit ADDLs neurotoxicity in hippocampal neurons via activation of the GluN2B -ERK1 /2 sig-naling pathways.

关 键 词：七氟烷 细胞外信号调节激酶1/2 GluN2B Aβ来源的扩散性配体(ADDLs) 阿尔茨海默病 

分 类 号：R34[医药卫生—基础医学] R741.02