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丰富环境联合褪黑素对SAMP8小鼠学习记忆功能及DNA氧化损伤的影响

Effects of enriched environment combined with melatonin on learning and memory function and DNA oxidative damage in SAMP8 mice
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摘要 目的探究丰富环境联合褪黑素对快速老化(SAMP8)小鼠学习记忆功能及DNA氧化损伤的影响。方法 6月龄SPF级健康雄性SAMP8小鼠24只,采用随机数字表法分为模型组、丰富环境组、褪黑素组和丰富环境+褪黑素组,每组6只;6只同源同月龄SAMR1小鼠为对照组。丰富环境组和丰富环境+褪黑素组小鼠饲养于丰富环境,同时褪黑素组、丰富环境+褪黑素组小鼠皮下注射褪黑素8 mg/(kg·d),模型组、对照组、丰富环境组小鼠皮下注射等体积0.9%氯化钠溶液,1次/d,共28 d。采用老化度评分评估小鼠老化情况;Morris水迷宫与Y迷宫实验评估小鼠学习记忆能力;苏木精-伊红染色法观察小鼠海马区细胞形态,免疫组织化学染色法检测小鼠海马区Aβ1-42蛋白水平;Western blot法、酶联免疫吸附法检测小鼠海马区DNA损伤标志蛋白磷酸化组蛋白H2A家庭成员X(γ-H2AX)、8-羟基脱氧鸟苷(8-OHdG)的水平。采用SPSS 25.0统计软件处理数据,多组间比较采用单因素方差分析,进一步两两比较采用LSD-t检验。结果 (1)5组小鼠干预后老化度评分差异有统计学意义(F=126.4,P<0.01)。干预后,丰富环境组、褪黑素组、丰富环境+褪黑素组小鼠老化度评分均低于模型组(均P<0.05),且丰富环境+褪黑素组小鼠显著低于丰富环境组(P<0.05)。(2)5组小鼠逃避潜伏期的时间-组别交互作用、组别主效应、时间主效应均显著(F=11.2,799.9,121.8,均P<0.01)。第2~4天,丰富环境组、褪黑素组、丰富环境+褪黑素组小鼠逃避潜伏期均显著低于模型组(P<0.05)。5组小鼠目标象限停留时间与跨平台次数均差异具有统计学意义(F=70.38,48.83,均P<0.01)。丰富环境组、褪黑素组、丰富环境+褪黑素组小鼠目标象限停留时间与跨平台次数显著高于模型组(均P<0.05)。(3)5组小鼠总交替次数及正确交替率均差异具有统计学意义(F=291.328,113.482,均P<0.01)。褪黑素组和丰富环境+褪黑素组小鼠 Objective To explore the effects of enriched environment combined with melatonin on learning and memory function and DNA oxidative damage in senescence accelerated mouse prone 8(SAMP8)mice.Methods Twenty-four 6-month-old SPF healthy male SAMP8 mice were randomly divided into model group,enriched environment group,melatonin group and enriched environment+melatonin group,with 6 mice in each group.Six homologous SAMR1 mice of the same age were used as the control group.The mice in the enriched environment group and the enriched environment+melatonin group were fed in the enriched environment.At the same time,the mice in the melatonin group and the enriched environment+melatonin group were subcutaneously injected with melatonin(8 mg/(kg·d))once a day for 28 d.The mice in the model group,the control group and the enriched environment group were subcutaneously injected with an equal volume of 0.9%sodium chloride solution once a day for 28 days.Aging score was used to evaluate the aging of mice.Morris water maze and Y maze tests were used to evaluate the learning and memory ability of mice.The cell morphology of hippocampus in mice was observed by hematoxylin-eosin staining,and the level of Aβ1-42 protein in hippocampus of mice was detected by immunohistochemical staining.The levels ofγ-H2A histone family member X(γ-H2AX)and 8-hydroxy-2 deoxyguanosine(8-OHdG)proteins in hippocampus of mice were detected by Western blot and Enzyme-linked immunosorbent assay.SPSS 25.0 statistical software was used to process the data.One-way analysis of variance was used for comparison among multiple groups,and LSD-t test was used for further pairwise comparison.Results(1)There was a statistical difference in aging scores among the 5 groups of mice after intervention(F=126.4,P<0.01).After intervention,the aging scores of mice in the enriched environment group,melatonin group,and enriched environment+melatonin group were lower than that in the model group(all P<0.05),and the score of the enriched environment+melatonin group was signifi
作者 屈海峰 杜鹃 李建民 王一超 王继成 罗光新 田子玉 刘俊杰 Qu Haifeng;Du Juan;Li Jianmin;Wang Yichao;Wang Jicheng;Luo Guangxin;Tian Ziyu;Liu Junjie(Clinical Medical College,North China University of Science and Technology,Tangshan 063000,China;School of Basic Medical Sciences,North China University of Science and Technology,Tangshan 063000,China;The Affilated Hospital,North China University of Science and Technology,Tangshan 063000,China;School of Public Health,North China University of Science and Technology,Tangshan 063000,China)
出处 《中华行为医学与脑科学杂志》 CAS CSCD 北大核心 2023年第11期968-975,共8页 Chinese Journal of Behavioral Medicine and Brain Science
基金 河北省2019年政府资助临床医学优秀人才培养和基础课题研究项目 唐山市科技计划项目(21130224C) 河北省2022年度医学科学研究课题计划(20221533) 华北理工大学"大学生创新创业训练计划项目"(X2022297)。
关键词 褪黑素 丰富环境 SAMP8小鼠 DNA氧化损伤 学习记忆功能 Melatonin Enriched environment SAMP8 mice DNA oxidative damage Learning and memory function
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