17β-雌二醇对创伤后应激障碍模型大鼠恐惧记忆再巩固期认知记忆的影响  

Effect of 17β-estradiol on cognitive memory during the reconsolidation period of fear memory in model rats with posttraumatic stress disorder

作　　者：王菡 左巧英 于昕琦 孙琳[1] 王玲 孙宏伟[1] Wang Han;Zuo Qiaoying;Yu Xinqi;Sun Lin;Wang Ling;Sun Hongwei(Department of Psychology,Weifang Medical University,Weifang 261053,China;Department of Bioscience and Technology,Weifang Medical University,Weifang 261053,China;Department of Clinical Medicine,Weifang Medical University,Weifang 261053,China;Medical Experiment and Training Center,Weifang Medical University,Weifang 261053,China)

机构地区：[1]潍坊医学院心理学院,潍坊261053 [2]潍坊医学院生命科学与技术学院,潍坊261053 [3]潍坊医学院临床医学院,潍坊261053 [4]潍坊医学院实验实训部,潍坊261053

出　　处：《中华行为医学与脑科学杂志》2023年第12期1064-1070,共7页Chinese Journal of Behavioral Medicine and Brain Science

基　　金：国家自然科学基金(82101588);山东省自然科学基金(ZR2020MC218);潍坊市科技发展计划项目(2022GX011)。

摘　　要：目的探讨海马源和性腺源17β-雌二醇(17β-estradiol,17β-E2)在创伤后应激障碍(post-traumatic stress disorder,PTSD)模型大鼠恐惧记忆再巩固期认知记忆的作用。方法采用8周龄清洁级雌性SD大鼠进行实验。采用单一连续刺激结合情景恐惧记忆制备大鼠PTSD模型。(1)性腺源雌二醇实验:50只雌性大鼠按照随机数字表法分为空白对照组、模型组、假卵巢去势组、卵巢去势组和卵巢去势+雌二醇组,每组10只。模型组、假卵巢去势组、卵巢去势组和卵巢去势+雌二醇组大鼠均进行PTSD造模,卵巢去势组和卵巢去势+雌二醇组大鼠进行卵巢切除,假卵巢去势组大鼠仅切除卵巢周围同质量的脂肪组织,卵巢去势+雌二醇组大鼠在卵巢去势7 d后注射17β-E2(1 mg/kg,1次/d,连续14 d)。(2)海马源雌二醇实验:40只雌性大鼠按照随机数字表法分为空白对照组、模型组、海马溶剂对照组、海马雌二醇抑制剂组,每组10只。模型组、海马溶剂对照组和海马雌二醇抑制剂组大鼠进行PTSD建模,海马雌二醇抑制剂组大鼠在恐惧记忆再巩固期内海马注射来曲唑1次(双侧,每侧0.5μL),海马溶剂对照组大鼠海马内注射二甲基亚砜1次(双侧,每侧0.5μL)。采用旷场实验和高架十字迷宫实验评价大鼠的焦虑水平和自主探索能力,僵住实验评价大鼠恐惧记忆水平,新物体识别实验评价大鼠非空间记忆水平。使用SPSS 25.0软件进行统计分析,多组间比较采用单因素方差分析,进一步两两比较采用LSD检验。结果(1)在性腺源雌二醇实验中,5组大鼠在旷场实验、高架十字迷宫实验、僵住实验和新物体识别实验中的各项指标均差异有统计学意义(F=20.200,12.702,7.514,10.094,7.899,13.211,均P<0.05)。模型组大鼠的直立次数、中心区域活动时间、进入开放臂距离和次数、认知指数均低于空白对照组(均P<0.05),僵住时间高于空白对照组(P<0.05)。卵巢去势+雌二醇ObjectiveTo explore the role of 17β-estradiol(17β-E2)derived from the hippocampus and gonad in the cognitive memory during the reconsolidation period of fear memory in rats with post-traumatic stress disorder(PTSD).MethodsThe 8-week-old clean grade female SD rats were used for this study.Single prolonged stress combined with context fear conditioning was used to prepare the rat PTSD model.(1)Gonad estradiol experiment:50 female rats were randomly divided into blank control group,model group,sham ovariectomy group,ovariectomy group,and ovariectomy+estradiol group by random number table method,with 10 rats in each group.The rats in model group,sham ovariectomy group,ovariectomy group,and ovariectomy+estradiol group were established PTSD model.Rats in ovariectomy group and ovariectomy+estradiol group underwent ovariectomy,while rats in sham ovariectomy group only were removed adipose tissue of the same mass around the ovaries.And the rats in ovariectomy+estradiol group were injected with 17β-E2(1 mg/kg,once a day for 14 days)7 days after ovariectomy.(2)Hippocampal estradiol experiment:40 female rats were randomly divided into blank control group,model group,hippocampal solvent control group and hippocampal estradiol inhibitor group by random number table method,with 10 rats in each group.The rats in model group,hippocampal solvent control group and hippocampal estradiol inhibitor group were established PTSD model.Rats in hippocampal estradiol inhibitor group were given letrozole once(bilateral,0.5μL per side)during the fear memory consolidation period and rats in the hippocampus solvent control group were injected once with dimethyl sulfoxide in the hippocampus(bilateral,0.5μL per side).The open field test and elevated cross maze test were used to evaluate the anxiety level and autonomous exploration ability,the freeze test was used to evaluate the fear memory,the new object recognition test was used to evaluate the non-spatial memory,and ELISA was used to detect serum 17β-E2 level.SPSS 25.0 software was used

关 键 词：创伤后应激障碍 恐惧记忆 记忆再巩固 17Β-雌二醇 来曲唑 海马 大鼠 

分 类 号：R749.5[医药卫生—神经病学与精神病学] R-332[医药卫生—临床医学]