亚慢性砷中毒小鼠大脑与小脑线粒体呼吸链相关基因的差异表达研究  

Characteristics of differentially expressed genes related to mitochondrial respiratory chain in the cerebrum and cerebellum of mice exposed to subchronic arseniasis

作　　者：洪岩[1] 朴丰源[1] 王艳艳[1] 刘鹏[1] 

机构地区：[1]大连医科大学劳动卫生与环境卫生学教研室,116044

出　　处：《中国地方病学杂志》2009年第6期622-625,共4页Chinese Jouranl of Endemiology

基　　金：国家自然科学基金（30571584）

摘　　要：目的应用毒理基因芯片技术观察三氧化二砷（As2O3）对小鼠大、小脑线粒体呼吸链相关基因表达谱的影响，为探讨砷的神经毒性机制提供特征性基因表达信息资料。方法30只昆明种小鼠按体质量随机分为对照组、低剂量组和高剂量组，每组10只，分别连续饮用含As2O3为0、1、4mg／L的蒸馏水60d。断头法处死小鼠，提取脑组织后，利用基因芯片技术检测小鼠脑组织线粒体相关基因表达谱的变化。结果与对照组比较，染砷组小鼠脑组织中差异表达的线粒体呼吸链相关基因共有26条。其中大脑线粒体呼吸链表达上调的基因有Ndufs4和Slc25a5，表达下调的基因有Ndufa12、Ndufab1、Ndufb2、Sdha、Uqcr、Cox6a2、Cox17、Atp5a1、Atp5g1、Atpif1和Slc25a3；小脑线粒体呼吸链表达上调的基因有Ndufa4、Ndufa6、Ndufs8、Atpif1和Slc25a1，表达下调的基因有Ndut08、Ndufa12、Sdha、Uqcr、Cox17、Atp5a1、Atp5g1和Slc25a3。结论亚慢性砷暴露可影响小鼠大脑和小脑线粒体呼吸链相关基因表达，尤其以诱导基因表达下调为主，其中对线粒体复合体I和复合体V各亚单位基因表达的影响较为明显。Objective To examine influence of arsenic trioxide（As2O3） on expression profiles of mitochondrial respiratory chain-related genes in the cerebrum and cerebellum of mice by GeneChip technique in order to provide the characteristic information of gene expressions for exploring the mechanism of As-induced neurotoxicity. Methods Thirty mice were divided into 3 groups with 10 for each, i.e., controls groups, low dose groups and high dose groups. As2O3（1 and 4 mg/L） was administered through distilled water for 60 days. Mice were decapitated and their brains were removed. Expression profiles of mitochondrial respiratory chain-related genes were examined in the brain of mice exposed to As2O3 by GeueChip. Results Compared with control groups, 26 mitochondrial respiratory chain-related genes in experimental groups were found in differential expression profiles. Expressions of Ndufs4 and Slc25a5 in mice cerebrum were significantly upregulated in the experimental groups, and expressions of Ndufa12, Ndufabl, Ndufb2, Sdha, Uqcr, Cox6a2, Cox17, Atp5a1, Atp5g1, Atpif1 and Slc25a5 in mice cerebrum were significantly downregulated. On the other hand, expressions of Ndufa4, Ndufa6, Ndufs8, Atpif1 and Slc25a1 in mice cerebellum were significantly upregulated in the experimental groups, and expressions of Ndufb8, Ndufa12, Sdha, Uqcr, Cox17, Atp5a1, Atp5g1 and Slc25a3 were significantly downregulated. Conclusions Subchronic exposure to As2O3 may affect expressions of mitochondrial respiratory chain-related genes in the brains of mice and induce mainly downregulation of these genes. Toxic effects of As2O3 on subunit gene expressions of mitochondrial complex I or complex V are more evident.

关 键 词：砷中毒 寡糖核苷酸序列分析 脑 DNA 线粒体 基因表达 

分 类 号：R686[医药卫生—骨科学]