[1]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.
 DENG Ping,CHEN Mengyan,XIE Jia,et al.Microarray analysis of the mechanism of liver injury induced by acute cadmium exposure in rats[J].J Third Mil Med Univ,2020,42(16):1641-1647.
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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(/HTML )
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《第三军医大学学报》[ISSN:1000-5404/CN:51-1095/R]

卷:
42卷
期数:
2020年第16期
页码:
1641-1647
栏目:
基础医学
出版日期:
2020-08-30

文章信息/Info

Title:
Microarray analysis of the mechanism of liver injury induced by acute cadmium exposure in rats
作者:
邓平陈梦妍谢佳田丽余争平皮会丰
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
Author(s):
DENG Ping CHEN Mengyan XIE Jia TIAN Li YU Zhengping PI Huifeng

Department of Occupational Health, Key Laboratory of Electromagnetic Radiation Protection of Ministry of Education, College of Military Preventive Medicine, Army Medical University (Third Military Medical University), Chongqing, 400038, China

关键词:
氯化镉大鼠肝毒性基因芯片细胞周期
Keywords:
CdCl2 rats hepatoxicity microarray cell cycle
分类号:
R575; R992; R995
文献标志码:
A
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(n=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(P<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PPI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(P<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(P<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:
ObjectiveTo explore the mechanism of acute cadmium (Cd) exposure-induced liver injury in rats. MethodsSixteen male SD rats were randomly divided into control group and acute cadmium exposure group (n=8), and received a single peritoneal injection of normal saline and 1.25 mg/kg CdCl2 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. ResultsCompared with the control rats, the rats with acute Cd exposure showed marked elevations of serum AST and ALT levels (P<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 analysis 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 (P<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 (P<0.05). ConclusionAcute 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.
 

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更新日期/Last Update: 2020-08-17