苯并芘暴露大鼠海马组织的全基因组DNA甲基化差异分析

谭强; 王晶; 李春林; 唐萍; 况桃; 黄强; 陈承志; 蒋学君; 程淑群; 涂白杰; 夏茵茵

doi:10.16016/j.1000-5404.201909139

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苯并芘暴露大鼠海马组织的全基因组DNA甲基化差异分析

基础医学 | 更新时间：2026-01-09

- 苯并芘暴露大鼠海马组织的全基因组DNA甲基化差异分析
- Genome-wide differential DNA methylation in hippocampus of rats after benzo(a)pyrene exposure
- 第三军医大学学报 2020年42卷第4期页码：359-366
- 作者机构：
  
  1.400016 重庆，重庆医科大学公共卫生与管理学院，医学与社会发展研究中心，健康领域社会风险预测治理协同创新中心
  2.611430 成都，四川省成都市新津县疾病预防控制中心
  3.400010 重庆，重庆医科大学附属第二医院预防保健科
- 作者简介：
  
  [夏茵茵，E-mail: 100118@cqmu.edu.cn XIA Yinyin, E-mail: 100118@cqmu.edu.cn
- 基金信息：
  
  国家自然科学基金面上项目(81502777);国家自然科学基金面上项目(81372957)
- DOI：10.16016/j.1000-5404.201909139
  中图分类号： R322.81; R394.1; R994.6
- 收稿：2019-09-18，
  
  修回：2019-12-10，
  
  纸质出版：2020-02-28
- 稿件说明：
移动端阅览
谭强, 王晶, 李春林, 等. 苯并芘暴露大鼠海马组织的全基因组DNA甲基化差异分析[J]. 第三军医大学学报, 2020,42(4):359-366.

Qiang TAN, Jing WANG, Chunlin LI, et al. Genome-wide differential DNA methylation in hippocampus of rats after benzo(a)pyrene exposure[J]. Journal of Third Military Medical University, 2020, 42(4): 359-366.
谭强, 王晶, 李春林, 等. 苯并芘暴露大鼠海马组织的全基因组DNA甲基化差异分析[J]. 第三军医大学学报, 2020,42(4):359-366. DOI： 10.16016/j.1000-5404.201909139.

Qiang TAN, Jing WANG, Chunlin LI, et al. Genome-wide differential DNA methylation in hippocampus of rats after benzo(a)pyrene exposure[J]. Journal of Third Military Medical University, 2020, 42(4): 359-366. DOI： 10.16016/j.1000-5404.201909139.

摘要

目的

研究苯并芘暴露大鼠海马组织的DNA甲基化差异，探讨苯并芘对海马功能损伤的机制。

方法

将大鼠分为对照组和苯并芘染毒组，每组10只；染毒结束后，采用Morris水迷宫检测大鼠的空间记忆学习能力，随后对大鼠海马进行HE染色与简化表观亚硫酸氢盐测序法(reduced representation bisulfite sequencing

RRBS)测序，对测序结果进行GO和KEGG分析，用qRT-P

CR检测

Tnr

基因与

Pla

基因mRNA的表达。

结果

Morris水迷宫与HE染色发现苯并芘暴露导致了大鼠空间学习记忆能力的障碍与海马组织损伤；RRBS测序后检测到差异性甲基化区域32个，GO分析富集到871条GO条目，KEGG分析得到52条通路，其中145条GO条目和11条通路显著富集(

0.05)，苯并芘染毒组与对照组相比，

Tnr

基因相对表达量减少，而

Pla

基因相对表达量增加(

0.05)。

结论

与未染毒的大鼠相比，苯并芘染毒后大鼠海马组织存在一定数量的甲基化差异位点，这些甲基化差异位点可能对研究苯并芘导致海马损伤的机制具有重要指导意义。

Abstract

Objective

To study the differential DNA methylation in the hippocampus of rats exposed to benzo(a)pyrene and explore the mechanism of benzo(a)pyrene-induced functional impairment of the hippocampus.

Methods

Twenty male SD rats (3 weeks old) were randomly divided into control group and benzo(a)pyrene exposure group (

=10)

and in the latter group

the rats were exposed to benzo(a)pyrene delivered

via

gavage on a daily basis for 7 consecutive weeks. After the exposure

Morris water maze test was performed to assess the changes in the spatial memory and learning ability of rats; the brain tissues were dissected for morphological examination of the hippocampal neurons with HE staining. Reduced representation bisulfite sequencing (RRBS) of the genomic DNA from the hippocampus was performed

followed by GO and KEGG analyses of the sequencing data; qRT-PCR was used to detect the expression levels of

Tnr

and

Pla

mRNAs.

Results

Morris water maze test and HE staining showed that exposure to benzo(a)pyrene resulted in obvious impairment of the spatial learning and memory abilities and caused hippocampal injuries in rats. DNA methylation sequencing identified 32 differentially methylated regions; GO analysis enriched 871 GO items and

KEGG analysis obtained 52 pathways

of which 145 GO items and 11 pathways were significantly enriched (

0.05). Compared with the control rats

the benzo(a)pyrene-exposed rats showed significantly decreased

Tnr

mRNA expression and increased

Pla

mRNA expressions in the hippocampus(

0.05).

Conclusion

A number of differentially methylated sites occur in the genomic DNA in rat hippocampus following benzo(a)pyrene exposure

and these sites may provide important clues in exploring the mechanism of benzo(a)pyrene-induced hippocampal injury.

关键词

Keywords

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