酒精对小鼠海马组织树突棘形态可塑性及记忆功能的影响  

Ethanol-induced memory impairment in mice by rac1 to influence morphological plasticity of dendritic spines

作　　者：李竹[1] 夏冰[1] 汪家文[1] 乐翠云[1] 王承飞 丁九阳 汪元河[1] LI Zhu;XIA Bing;WANG Jiawen;LE Cuiyun;WANG Chengfei;DING Jiuyang;WANG Yuanhe(School of Forensic Medicine,Guizhou Medical University,Guiyang 550004,Guizhou,China)

机构地区：[1]贵州医科大学法医学院,贵州贵阳550004

出　　处：《贵州医科大学学报》2021年第3期316-321,共6页Journal of Guizhou Medical University

基　　金：贵阳市科技计划项目[黔科合LG字(2012)030];国家自然科学基金项目(81660309);贵州省科技厅基金项目[黔科合平台人才(2018)5779-3];贵州省大学生创新创业训练计划项目(20195200922,20195200138)。

摘　　要：目的探讨酒精对小鼠海马组织树突棘形态可塑性及记忆功能的影响。方法15只野生型C57BL/6雄性小鼠随机分成对照组(Control,Con组)、单纯酒精处理组(Ethanol,Et组,给予小鼠20%乙醇2 mL/kg、每天1次,持续2周)及EHOP016治疗组(Et+EHOP016组,给予小鼠20%乙醇2 mL/kg后,立即灌胃EHOP016、持续2周),采用Morris水迷宫实验检测小鼠记忆能力,卢色黄胞内注射检测小鼠海马区域树突棘数量,免疫蛋白印迹法检测小鼠海马脑区Ras相关的C3肉毒杆菌毒素底物1-三磷酸鸟苷(Rac1-GTP)、C3肉毒杆菌毒素底物1总蛋白(Total Rac1)、突触素I(Synapsin I)、突触体素(Synatophysin)和突触后致密蛋白95(PSD95)表达。结果与Con组比较,乙醇处理可明显激活海马Et组小鼠树突棘数量减少、Synapsin I及Synatophysin水平降低,水迷宫实验显示小鼠记忆能力降低;与Et组比较,EHOP016组小鼠海马组织Rac1-GTP水平明显降低、减轻酒精导致的小鼠记忆能力的损伤、抑制酒精导致的成熟型树突棘数量的减少、上调酒精导致的突触相关蛋白的减少。结论酒精可能通过激活Rac1来减少树突棘数量,从而导致记忆功能损害。Objective To investigate the effect of ethanol on the morphological plasticity and memory function of dendritic spines in mice hippocampus.Methods Fifteen wild-type C57BL/6 male mice were randomly divided into control group(CON),ethanol treatment group(ET)and EHOP016 treatment group(ET+EHOP016).Mice in the ET group were given 20%ethanol(2 mL/kg)once a day for 2 weeks,and mice in the ET+EHOP016 group after intraperitoneal injection of 20%ethanol(2 mL/kg)and ehop016(10 mL/kg)were given by gavage immediately for 2 weeks.Morris water maze test was used to test the memory ability of mice.Fluorescein was injected into the pyramidal layer cells of mice hippocampus to detect the number of dendritic spines in the hippocampus.Western Blot was used to detect the expression of Rac1 GTP,Rac1,Synapsin I,Synaptophysin,PSD95 protein,Ras-related C3 botulinum toxin substrate 1-guanosine triphosphate in the hippocampus(Rac1-GTP),C3 botulinum toxin substrate 1 Total protein(Total Rac1),Synapsin I,Synatophysin,and Postsynaptic Density Protein 95(PSD95)in the hippocampus of mice.Results Compared with CON group,ethanol treatment significantly reduced the number of dendritic spines,Synapsin I and Synatophysin levels in hippocampal ET group.The Water maze test showed that the memory ability of mice was reduced.Compared with ET group,the RAC1-GTP level in hippocampal tissues of mice in EHOP016 group was significantly decreased,which alleviated the damage of memory ability,inhibited the reduction of mature dendritic spines and the decrease of synaptic related proteins induced by alcohol up-regulation.Conclusions Ethanol may reduce the number of dendritic spines by activating RAC1 and lead to impaired memory function in mice.

关 键 词：树突棘 酒精 记忆损伤 Ras相关的C3肉毒杆菌毒素底物1 

分 类 号：R338[医药卫生—人体生理学]