壬基酚致雄性仔鼠脑组织差异基因的表达

Deleterious Effects of Nonylphenol on Profile of Gene Expression in Hippocampus of Weaning Male Rats

目的应用基因芯片技术,检测壬基酚暴露对仔鼠脑组织差异基因的表达,筛选部分与神经毒性相关的差异表达基因及通路进行进一步机制研究。方法建立孕期和哺乳期暴露壬基酚的仔鼠模型,提取暴露组和对照组出生21 d仔鼠脑组织mRNA,采用Roche Nimblegen公司生产的12×135位点的包含大鼠26 419个基因的表达谱基因芯片,检测脑基因的表达,扫描仪进行扫描及数据处理。结果暴露组与对照组共有1 254个差异表达基因,其中619个基因上调,635个基因下调。部分与神经系统功能相关差异表达基因为:1神经营养相关的基因:甘丙肽基因下调,神经生长因子基因下调;2细胞凋亡的相关基因:凋亡蛋白酶活化因子-1基因上调,凋亡抑制基因-1基因下调,半胱氨酸蛋白酶7基因上调;3信号传递及离子通道相关基因的表达:谷氨酸盐受体基因下调,钙调素依赖性蛋白激酶Ⅱ基因下调。结论壬基酚能导致仔鼠海马神经元信号传导、免疫应答、细胞凋亡、炎症反应因子、神经胶质细胞发育等相关基因的差异表达,以上改变有可能干扰神经系统的发育和功能。

Objectives To investigate the differential gene expression in hippocampus of nonylphenol （NP）-treated and control weaning rats and to screen part of neurotoxicity-related differential expression genes with gene chip technology for further verification. Methods Establishing animal models for NP exposure （100 mg/kg· day） during gestation and lactation, mRNA of hippocampus in NP-treated group and control group were isolated at 21 days after birth and the differential gene expression was examined by gene chip technology. The DNA microarrays were scanned by Axon GenePix 4 000 B scanner and the fluorescent values were analyzed by GenePix Pro software （4.1.1.31 Axon）. Results Differentially expressed genes were identified by cDNA microarray. Among the 1 254 genes screened out, 619 genes were up-regulated and 635 genes were down-regulated. The responsibilities of part differentially expressed genes have been understood： （1） Neurotrophy-related genes： Nerve growth factor （NGF） gene was down-regulated, galanin （Gal） gene was down-regulated, and growth associated protein 43 （GAP43） gene was down-regulated. （2）Apoptosis-related genes： Apoptotic protease activating factor-1 （Apaf-1） gene was up-regulated, cysteine-aspartic acid protease （Caspase 7） gene was up-regulated, and the defender of apoptosis death-1 （DAD1） gene was down - regulated. ~Signal transduction-related and ion channel-related genes： Glutamate receptor （AMPA2） gene was down-regulated, ealcium/calmodulin-dependent protein kinase II delta （Camk2d） ion transport-related genes was down-regulated. Conclusions Exposure to NP during gestation and lactation might involve in influencing neurotrophy-related, signal transduction-related and ion channel-related as well as apoptotic factor-related differential gene expression in hippoeampus neurons, which might have effects on interfering the function and development of CNS in pups.