基于基因芯片分析急性镉暴露致大鼠肝损伤及其可能机制

邓平; 陈梦妍; 谢佳; 田丽; 余争平; 皮会丰

doi:10.16016/j.1000-5404.202004185

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基于基因芯片分析急性镉暴露致大鼠肝损伤及其可能机制

基础医学 | 更新时间：2026-01-09

- 基于基因芯片分析急性镉暴露致大鼠肝损伤及其可能机制
- Microarray analysis of the mechanism of liver injury induced by acute cadmium exposure in rats
- 第三军医大学学报 2020年42卷第16期页码：1641-1647
- 作者机构：
  
  400038重庆，陆军军医大学(第三军医大学)军事预防医学系军队劳动卫生学教研室，电磁辐射医学防护教育部重点实验室
- 作者简介：
  
  [ 皮会丰，E-mail:pihuifeng2010@163.com PI Huifeng, E-mail:pihuifeng2010@163.com
- 基金信息：
  
  国家自然科学基金青年科学基金(81703267);重庆英才·青年拔尖人才(CQYC201905014);重庆市自然科学基金(CSTC2018jcyjAX0138)
- DOI：10.16016/j.1000-5404.202004185
  中图分类号： R575;R992;R995
- 收稿：2020-04-17，
  
  修回：2020-06-04，
  
  纸质出版：2020-08-30
- 稿件说明：
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邓平, 陈梦妍, 谢佳, 等. 基于基因芯片分析急性镉暴露致大鼠肝损伤及其可能机制[J]. 第三军医大学学报, 2020,42(16):1641-1647.

Ping DENG, Mengyan CHEN, Jia XIE, et al. Microarray analysis of the mechanism of liver injury induced by acute cadmium exposure in rats[J]. Journal of Third Military Medical University, 2020, 42(16): 1641-1647.
邓平, 陈梦妍, 谢佳, 等. 基于基因芯片分析急性镉暴露致大鼠肝损伤及其可能机制[J]. 第三军医大学学报, 2020,42(16):1641-1647. DOI： 10.16016/j.1000-5404.202004185.

Ping DENG, Mengyan CHEN, Jia XIE, et al. Microarray analysis of the mechanism of liver injury induced by acute cadmium exposure in rats[J]. Journal of Third Military Medical University, 2020, 42(16): 1641-1647. DOI： 10.16016/j.1000-5404.202004185.

摘要

目的

研究急性镉暴露致大鼠肝损伤及其可能机制。

方法

16只SPF级雄性SD大鼠(250~300 g)分为对照组和实验组(

=8)。实验组采用一次性腹腔注射氯化镉溶液，剂量为1.25 mg/kg·bw

对照组注射等量的生理盐水。24 h后处死

采集大鼠血清并摘取肝脏。HE染色观察肝脏组织病理变化。生化分析仪检测血清中丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)含量。基因数据库寻找到相同实验条件下肝组织芯片GSE65198

在线软件GEO2R获得差异表达基因(DEGs)，差异基因行GO功能注释和KEGG富集分析

蛋白-蛋白相互作用(PPI)及cytoHubba软件构建交互网络，寻找并验证核心基因。

结果

相比于对照组，镉暴露组大鼠肝脏并没有炎症细胞浸润、肝细胞气球样变、坏死等明显的病理学变化，但是其血清中ALT和AST的表达显著增高(

0.01)。GO及KEGG分析显示DEGs首要参与了细胞周期阻滞。Cdc20、Ccnb1、Cdk1、Top2a、Ube2c是DEGs的P

PI网络中的核心基因。相比于对照组，5个核心基因的mRNA水平在镉暴露的肝脏中显著降低(

0.01)，但是参与细胞周期的3个hub基因Cdc20、Ccnb1、Cdk1中仅Cdk1的蛋白表达水平在镉暴露组中显著降低(

0.05)。

结论

急性镉暴露显著抑制肝细胞的细胞周期从而诱导大鼠肝脏损伤，Cdk1等核心基因可能是镉抑制细胞周期的重要靶点。

Abstract

Objective

To explore the mechanism of acute cadmium (Cd) exposure-induced liver injury in rats.

Methods

Sixteen male SD rats were randomly divided into control group and acute cadmium exposure group (

=8)

and received a single peritoneal injection of normal saline and 1.25 mg/kg CdCl

dissolved in normal saline

respectively. The rats were euthanized at 24 h after the injection for histopathological assessment using HE staining and detection of serum alanine transaminase (ALT) and aspartate transaminase (AST) activities using a biochemical analyzer. The tissue microarray GSE65198 dataset from the GEO database was analyzed for the gene expression profiles in the liver tissues of rats receiving identical treatments

and online analysis with GEO2R was performed to compare the data between the control and daily 1.25 mg/kg cadmium exposure group to identify the differentially expressed genes (DEGs). The functions and pathway enrichment of the DEGs were analyzed using Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The hub genes were identified by protein-protein interactions (PPIs) network and Cytoscape software

and their expression levels in the liver tissues of the rats were verified by qRT-PCR.

Results

Compared with the control rats

the rats with acute Cd exposure showed marked elevations of serum AST and ALT levels (

0.01) without exhibiting obvious pathologies in the liver tissues

where no ballooning hepatocyte degeneration

focal necrosis or inflammatory cell infiltration was found. GO and KEGG enrichment analy

sis confirmed that the DEGs were highly enriched in cell cycle arrest (the Top 1 signaling pathway). Cdc20

Ccnb1

Cdk1

Top2a

and Ube2c were the hub genes in the PPI network of the DEGs

all of which showed decreased expression at the mRNA level in the liver of rats with acute Cd exposure (

0.01). Only Cdk1 out of the 3 hub genes involved in cell cycle (Cdc20

Ccnb1

and Cdk1) was significantly down-regulated following cadmium exposure in rats (

0.05).

Conclusion

Acute Cd exposure induces liver injuries in rats by causing cell cycle arrest of the hepatocytes

and Cdk1

along with other hub genes

may play important roles in Cd-induced cell cycle arrest.

关键词

Keywords

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