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首页 > 过刊浏览>2023年第31卷第9期 >1133-1139. DOI:10. 3969 / j.issn.1005-4847. 2023. 09. 004
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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
作者:
作者单位:

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


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

1.Research Base of TCM Syndrome, Fujian University of Chinese Medicine, Fuzhou 350122, China. 2. Fujian Key Laboratory of TCM Health State, Fujian University of Chinese Medicine, Fuzhou 350122

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    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。

    Abstract:

    Objective To investigate the effect of perimenopausal depression on the expression of important genes in the Notch1 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 Notch1 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 Notch1 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 Jagged1, Notch1, and Hes5 in the Notch1 signaling pathway was significantly downregulated in the hippocampus of perimenopausal depression rats (P< 0. 01 orP< 0. 05). Some methylation sites and rates of the Hes5 gene were increased significantly, whereas the methylation sites and rates of Jagged1 and Notch1 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.

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沈建英,梁文娜,陈惠芳,张凌媛,庄垸荧,陈晓阳,陈雅茹,肖琼琼,杨敏,闵莉,龚琳.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[J].中国实验动物学报,2023,31(9):1133~1139.

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  • 收稿日期:2023-03-24
  • 在线发布日期: 2023-12-29
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