砷对小鼠小脑神经递质传递相关基因表达影响的基因芯片研究

Study on expression of neurotransmitter transmission-related genes in cerebellum of mice exposed to arsenic by gene chip technology

关键词:  三氧化二砷  基因芯片  小脑  神经递质传递  差异表达基因

Key words:  As2O3  genechip  cerebellum  neurotransmitter transmission  differential expression gene

摘要:

［目的］应用基因芯片技术观察砷对小鼠小脑神经递质传递相关基因表达谱的影响，为探讨砷的神经毒性机制提供分子毒理学依据。［方法］昆明种小鼠30只，随机分为3组，即饮用水对照组、低剂量染砷组（1 mg/L As₂O₃）和高剂量染砷组（4 mg/L As₂O₃），连续染毒60 d，断头法处死小鼠，利用基因芯片技术检测小脑组织神经递质的分泌、转运及膜受体相关基因表达谱的变化。［结果］基因芯片筛选结果显示，与对照组比较，染砷组小脑组织中差异表达2倍及以上的神经递质传递相关基因有17条。其中，表达下调的基因有10条，包括Tph2、Gria2、Grin1、Gabrb2、Camk4、Nrxn1、Lin7c、Nrxn3、Syt1及Cpix2；表达上调的基因有7条，包括Slc6a2、Slc6a5、Slc6a11、SLc18a2、Slc18a3、Htr2c和Lin7b。［结论］慢性砷暴露可影响小鼠小脑神经递质传递相关基因的表达。

Abstract:

［Objective］To provide molecular toxicological evidences for exploring the mechanism of arsenic-induced neurotoxicity.［Methods］Thirty mice were divided into 3 groups, e.g., one controls and 2 experimental groups (1 and 4 mg/L As₂O₃). As₂O₃was administered through drinking water for 60 days, followed by decollation. Expression profiles of neurotransmitter transmission-related genes, including secretion-related genes and transport-related genes as well as receptor activity-related genes were examined in the cerebellum of these mice by genechip technology.［Results］Seventeen neurotransmitter tansmission-related genes in experimental groups were found in differential expression profile, including 10 downregulated genes. Tph2,Gria2, Grin1, Gabrb2, Camk4, Nrxn1, Lin7c, Nrxn3, Syt1 and Cpix2 and 7 upregulated genes Slc6a2, Slc6a5, Slc6a11, SLc18a2, Slc18a3, Htr2c and Lin7b.［Conclusions］Chronic exposure to arsenic may affect expressions of neurotransmitter transmission-related genes in the cerebullum of mice.