多环芳烃暴露致学习记忆改变过程中的microRNA差异表达研究

项目名称： 多环芳烃暴露致学习记忆改变过程中的microRNA差异表达研究

项目编号： No.81502795

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 王芳

作者单位： 山西医科大学

项目金额： 18万元

中文摘要： 学习记忆功能下降是多环芳烃神经毒性最突出的表现，但具体机制尚不清楚。microRNA可以介导环境因素对氧化应激的应答反应，并可通过抑制靶基因的表达调控神经递质的合成，对学习和记忆过程具有重要作用，因此我们推测microRNA可能在多环芳烃神经毒性中发挥作用。本研究将采用miRNA芯片技术和实时定量PCR筛选多环芳烃职业暴露人群外周血差异表达的microRNA，分析多环芳烃致学习记忆改变与miRNA 差异表达的关系，并建立多环芳烃暴露致学习记忆改变的大鼠模型，探讨多环芳烃暴露对大鼠脑组织microRNA表达、氧化应激水平及神经递质含量改变间的影响，分析microRNA在多环芳烃暴露致学习记忆功能下降中的调节作用及其可能机制，为深入研究多环芳烃神经毒性的表观遗传机制提供基础，并为寻找职业多环芳烃暴露致神经毒性的分子标志物提供依据。

中文关键词： 多环芳烃；微小RNA；氧化应激；神经递质；神经毒性

英文摘要： Learning and memory deficits are the most prominent manifestation of neurotoxicity caused by polycyclic aromatic hydrocarbons (PAHs) exposure, but the mechanism remains unclear. MicroRNAs play an important regulatory role in learning and memory processes through mediating oxidative stress induced by environmental factors and regulating the synthesis of neurotransmitter by inhibiting target gene expression. The purpose of the research is to examine whether microRNAs attribute to PAHs-induced neurotoxicity on learning and memory. Workers occupationally exposed or unexposed to PAHs are to be selected as subjects. Both miRNA microarray analysis and RT-PCR will be performed to determine the change of miRNA expression in blood leukocyte. Rat model of PAHs exposure is to be established to investigate the effects on miRNA expression, oxidative stress and the content of neurotransmitter in brain. Collectively, potential regulatory role of miRNA will be explored on impaired learning and memory induced by PAHs. The study is intended to provide better insight into the epigenetic mechanisms of PAHs-induced learning and memory injury, and also to provide a basis for looking for molecular biomarkers of PAHs-induced neurotoxicity.

英文关键词： polycyclic aromatic hydrocarbon;microRNA;oxidative stress;neurotransmitter;neurotoxicity