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[产前暴露于苯并[a]芘诱导的子代肝细胞基因表达模式]

[Gene expression patterns of offsprings' hepatocytes induced by prenatal Benzo[a]pyrene exposure].

作者信息

Wang Qin, Li Na, Wang Jun, Pan Li-jun, Huang Li-hua, Jin Yin-long

机构信息

Institute for Environmental Health and Related Product Safety, Chinese Center for Disease Control and Prevention, Beijing 100021, China.

出版信息

Zhonghua Yu Fang Yi Xue Za Zhi. 2013 Apr;47(4):352-7.

Abstract

OBJECTIVE

To study the gene expression patterns in livers of infant rats after Benzo[a]pyrene (BaP) exposure during pregnancy and explore the important gene and signaling pathways in the toxic mechanism of BaP.

METHODS

Thirty-two pregnant SD rats were randomly divided into four groups: vehicle control (corn oil) and treatment groups (0.75, 1.50 and 3.00 mg/kg BaP in corn oil). BaP solutions were given by gastric infusion from the 3rd to the 17th day of pregnancy. After delivery the offspring's liver were taken to detect the gene expression by RatRef-12 gene chip. The stability of gene chip was tested by repeated experiments.

RESULTS

After prenatal BaP exposure 1232 genes with different expression variations in hepatocytes of offsprings were identified. Three expression patterns of genes related to the dose of prenatal BaP exposure were identified with significant difference (P < 0.05). As the dose of prenatal BaP exposure increased, the gene expression patterns were downregulated, upregulated, and fluctuated. Twenty-six signaling pathways with differently expressed genes mainly focused on: growth and development, toxicant metabolism and inflammation (P < 0.05). The data from gene network analysis demonstrated that CYP2C13, GSTO1, Rela, MAPK8 and Plcg1 were the key genes in the gene network.

CONCLUSION

Gene expression patterns of offsprings' hepatocytes were influenced by prenatal BaP exposure. Some key genes and signal pathways were also found. The study provides an important clue for the toxicity and mechanisms of the prenatal BaP exposure on the growth and development of offspring.

摘要

目的

研究孕期苯并[a]芘(BaP)暴露后幼鼠肝脏中的基因表达模式,探讨BaP毒性机制中的重要基因和信号通路。

方法

将32只孕SD大鼠随机分为四组:溶剂对照组(玉米油)和处理组(玉米油中分别含0.75、1.50和3.00 mg/kg BaP)。在妊娠第3天至第17天经胃灌注给予BaP溶液。分娩后取子代肝脏,用RatRef-12基因芯片检测基因表达。通过重复实验检测基因芯片的稳定性。

结果

产前BaP暴露后,子代肝细胞中鉴定出1232个表达有差异的基因。确定了与产前BaP暴露剂量相关的三种基因表达模式,差异有统计学意义(P < 0.05)。随着产前BaP暴露剂量增加,基因表达模式呈下调、上调和波动变化。26条基因表达有差异的信号通路主要集中在生长发育、毒物代谢和炎症方面(P < 0.05)。基因网络分析数据表明,CYP2C13、GSTO1、Rela、MAPK8和Plcg1是基因网络中的关键基因。

结论

产前BaP暴露影响子代肝细胞的基因表达模式,还发现了一些关键基因和信号通路。本研究为产前BaP暴露对子代生长发育的毒性及机制提供了重要线索。

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