5-Aza-cdR通过DNA甲基化调节BDNF参与学习记忆的机制  

5-Aza-cdR regulates the expression of BDNF to participation in learning and memory of mice through DNA methylation

作　　者：张世纪 付翁 贾小娥 巴德仁贵[1,3] 姜树原[1] 谢雅彬 霍东升[2] 谢伟[1,3] 刘晓蕾[1] 邵国[1,3] ZHANG Shiji;FU Weng;JIA Xiao’e;BADE Rengui;JIANG Shuyuan;XIE Yabin;HUO Dongsheng;XIE Wei;LIU Xiaolei;SHAO Guo(Inner Mongolia Key Laboratory of Hypoxic Translational Medicine,Baotou Medical College,Baotou 014040,China;School of Basic Medicine and Forensic Sciences,Baotou Medical College;School of Medical Technology and Anesthesia,Baotou Medical College of Neuroscience Institute,Baotou Medical College)

机构地区：[1]包头医学院内蒙古自治区低氧转化医学重点实验室,内蒙古包头014040 [2]包头医学院基础医学与法医学院 [3]包头医学院医学技术与麻醉学院神经科学研究所

出　　处：《包头医学院学报》2022年第1期21-25,共5页Journal of Baotou Medical College

基　　金：国家自然科学基金项目(82071479,31860307);内蒙古自然科学基金项目(2020MS08171,2020MS08172,2020MS08006);内蒙古自治区高等学校“青年科技英才支持计划”项目(NJYT-18-B26);内蒙古自治区高等学校科学研究项目(NJZZ19189,NJZY17250);内蒙古自治区研究生科研创新项目(SZ2020051)。

摘　　要：目的:研究5-氮-2’脱氧胞苷(5-Aza-cdR)通过影响DNA甲基转移酶功能,调节BDNF表达并参与学习记忆的相关机制。方法:以70只6~8周18~22克雄性ICR小鼠为研究对象,随机分为三组:注射PBS为C组,25只;注射5-Aza-cdR为注射组,30只;注射K252a为K252a注射组,15只。通过Western blot、real-time PCR、免疫荧光技术,检测小鼠海马脑区DNA甲基转移酶3B(DNMT3B)和脑源性神经营养因子(BDNF)在mRNA和蛋白水平的表达变化,通过水迷宫实验检测小鼠的学习记忆能力。结果:与C组比较,小鼠经过5-Aza-cdR处理24 h后,DNMT3B的蛋白水平和mRNA水平均有所下降(P<0.05),BDNF的蛋白和mRNA水平显著增加(P<0.05)。与C组比较,5-Aza-cdR注射组的BDNF荧光强度显著增强(P<0.05),小鼠找到目标平台的潜伏期显著降低(P<0.05),目标象限百分比以及目标象限穿越次数均显著增加(P<0.05)。结论:5-Aza-cdR下调DNMT3B表达后,通过上调小鼠海马中BDNF的表达,可提高小鼠的学习记忆能力。Objective:To study the correlation mechanism of 5-nitrogen-2'deoxycytosine(5-Aza-cdR)by affecting DNA methyltransferase function,regulating BDNF expression and participating in learning and memory.Methods:Seventy male ICR mice(6-8 weeks,18-22 grams)were randomly divided into three groups:25 mice in group C were injected with PBS;30 mice in the injection group were injected 5-Aza-cdR;15 mice in K252a injection group were injected with K252a.The expression changes of DNA methyltransferase 3B(DNMT3B)and brain-derived neurotrophic factor(BDNF)in the hippocampus of mice at mRNA and protein levels were detected by Western blot,real-time PCR and immunofluorescence.The learning and memory ability of mice was detected by water maze test.Results:Compared with group C,the protein and mRNA levels of DNMT3B were significantly decreased(P<0.05),and the protein and mRNA levels of BDNF were significantly increased(P<0.05)after treatment with 5-Aza-cdR for 24 h.Compared with group C,the fluorescence intensity of BDNF in the 5-Aza-cdR injection group was significantly enhanced(P<0.05),the latency for mice to find the target platform was significantly reduced(P<0.05),and the percentage of target quadrant and the number of target quadrant crossings were significantly increased(P<0.05).Conclusion:After 5-Aza-cdR down-regulated DNMT3B expression,the learning and memory ability of mice could be improved by up-regulating the expression of BDNF in the hippocampus of mice.

关 键 词：5-氮-2’脱氧胞苷 DNA甲基转移酶3B 脑源性神经营养因子 学习记忆 

分 类 号：R73[医药卫生—肿瘤]