围绝经期抑郁症大鼠海马Notch1信号通路基因的表达与甲基化水平研究  

Expression and methylation level of hippocampal Notch1 signaling pathway genes in perimenopausal depression rats

作　　者：沈建英[1,2] 梁文娜 陈惠芳[1,2] 张凌媛 庄垸荧[1] 陈晓阳 陈雅茹[1] 肖琼琼 杨敏 闵莉 龚琳 SHEN Jianying;LIANC Wena;CHEN Hufang;ZHANG Lingyan;ZHUANG Yuanying;CHEN Xiaoyang;CHEN Yaru;XIAO Qiongqiong;YANG Min;MIN Li;CONG Lin(Research Base of TCM Syndrome,Fujian University of Chinese Medicine,Fuzhou 350122,China;Fujian Key Laboratory of TCM Health State,Fujian University of Chinese Medicine,Fuzhou 350122)

机构地区：[1]福建中医药大学中医证研究基地,福州350122 [2]福建省中医健康状态辨识重点实验室,福州350122

出　　处：《中国实验动物学报》2023年第9期1133-1139,共7页Acta Laboratorium Animalis Scientia Sinica

基　　金：国家自然科学基金项目(82174248,82274409);福建省自然科学基金项目(2022J01362);福建中医药大学校管课题(X2021024);福建中医药大学基础类学科科研提升计划项目(XJC2022012);2022年大学生创新创业训练计划(202210393004,S202210393009,S202210393026)。

摘　　要：目的 从表观遗传学之基因启动子DNA甲基化角度探讨围绝经期抑郁症对大鼠海马Notch1信号通路关键基因表达及其启动子DNA甲基化的影响。方法 将12月龄雌性围绝经期SD大鼠随机分为对照组和模型组。分别采用旷场实验和糖水消耗实验进行焦虑样及抑郁样的行为学评价。采用实时荧光定量PCR法(real time quantitative PCR,RT-qPCR)检测大鼠海马Notch1信号通路关键基因的表达。运用重亚硫酸氢盐测序(bisulfite sequencing PCR,BSP)法分析Notch1信号通路关键基因启动子区的甲基化位点及其甲基化水平。结果 围绝经期抑郁症大鼠旷场实验水平得分和垂直得分及糖水消耗率均显著下降;围绝经期抑郁症大鼠海马组织中Notch1信号通路关键基因Jagged1、Notch1和Hes5的表达均显著下调(P<0.01或P<0.05);其中Hes5基因的部分甲基化位点及其甲基化率均显著增加,而Jagged1和Notch1基因的甲基化位点及其甲基化率差异均无统计学意义(P>0.05)。结论 围绝经期抑郁症大鼠海马Notch1信号通路关键基因表达显著下调,其中Hes5基因表达下调可能与其启动子DNA甲基化水平上升有关。Objective To investigate the effect of perimenopausal depression on the expression of important genes in the Notchl signaling pathway and DNA methylation of their promoters in the rat hippocampus from the perspective of DNA methylation of epigenetics.Methods Twelve-month-old female SD rats were randomly divided into control and model groups.Anxiety-and depression-like behavioral evaluations were conducted on rats using open field and sugar consumption tests,respectively.Real time quantitative PCR(RT-qPCR)was used to measure the expression of important genes in the Notchl signaling pathway in the hippocampal dentate gyrus.Bisulfite sequencing was used to analyze methylation sites and levels in the promoter regions of important genes in the Notchl signaling pathway.Results In perimenopausal depression rats,horizontal and vertical scores of the open field test and the rate of sucrose consumption were decreased significantly.Expression of important genes Jaggedl,Notchl,and Hes5 in the Notchl signaling pathway was significantly downregulated in the hippocampus of perimenopausal depression rats(P<0.01 or P<0.05).Some methylation sites and rates of the Hes5 gene were increased significantly,whereas the methylation sites and rates of Jaggedl and Notchl genes were not significantly different(P>0.05).Conclusions The expression of important genes in the Notch1 signaling pathway in the hippocampal dentate gyrus of perimenopausal depression rats is significantly downregulated,and downregulation of the Hes5 gene may be related to the increase in the promoter DNA methylation level.

关 键 词：围绝经期 抑郁症 海马 Notch1信号通路 DNA甲基化 

分 类 号：Q95-33[生物学—动物学]