甲基苯丙胺成瘾大鼠中枢及血浆中差异表达microRNA的发现

发布时间：2018-04-18 08:43

本文选题：药物成瘾 + 甲基苯丙胺　；参考：《中南大学》2013年硕士论文

【摘要】：目的药物成瘾是一种反复发作的慢性脑疾病。而苯丙胺类兴奋剂作为新型毒品滥用趋势更加严峻。发现与苯丙胺类兴奋剂成瘾密切相关的新分子具有重要的科学意义和潜在应用价值。本文的研究目的即为发现与甲基苯丙胺成瘾阶段密切相关的差异表达microRNA,研究其在成瘾不同阶段中发挥的潜在调控作用,探讨其作为候选生物标志物的可能性,为药物成瘾神经生物学机制的阐明及苯丙胺类兴奋剂成瘾的诊断和治疗提供线索。方法 1.通过右颈静脉插管手术建立甲基苯丙胺诱发的大鼠自身给药模型,进行获得性给药训练和递增性给药训练。 2.采用miRNA表达谱芯片及SYBR Green实时定量PCR对成瘾相关脑区中miRNA的差异表达水平进行筛选验证。结合生物信息学分析对候选miRNA及预测靶分子进行功能定位,确定候选分子。 3.采用实时定量PCR方法检测血浆中循环]miRNA。结果 1.建立了能够很好模拟人类药物成瘾行为特征的大鼠甲基苯丙胺自身给药模型,为研究甲基苯丙胺成瘾的神经生物学机制奠定了基础。 2.在具有规律性用药特征或强迫性用药特征的甲基苯丙胺成瘾大鼠的背侧纹状体和前额叶皮层中分别发现了12个和8个可能发生差异表达的miRNA分子；生物信息学分析显示miR-x6等11个差异表达的miRNA及其靶分子的功能可能与甲基苯丙胺成瘾及其神经毒性相关,值得深入研究。 3.循环miR-x18在具有强迫性用药特征的甲基苯丙胺成瘾大鼠中存在下调趋势；而循环miR-x19两给药组中均呈上调。结论综上所述,本文建立了能够较好模拟人类成瘾行为特征的大鼠甲基苯丙胺自身给药模型,在成瘾动物的背侧纹状体和前额叶皮层中发现了19个可能发生差异表达的miRNA分子,在血浆中发现了2个可能发生差异表达的循环miRNA分子,为研究miRNA在甲基苯丙胺成瘾中的作用、以及循环miRNA作为甲基苯丙胺成瘾诊断的候选生物标志物的研究提供了线索。
[Abstract]:Objective Drug addiction is a recurrent chronic brain disease.The trend of amphetamine-type stimulants as a new type of drug abuse is more severe.The discovery of new molecules closely related to amphetamine-type stimulant addiction has important scientific significance and potential application value.The purpose of this study was to find differentially expressed microRNAs closely related to the stage of methamphetamine addiction, to study the potential regulatory role of microRNAs in different stages of addiction, and to explore the possibility of using microRNAs as candidate biomarkers.It provides clues for the elucidation of neurobiological mechanism of drug addiction and the diagnosis and treatment of amphetamine-type stimulants addiction.Method1.The model of methamphetamine induced self-administration was established by right jugular vein intubation in rats.2.MiRNA expression microarray and SYBR Green real-time quantitative PCR were used to screen and verify the differential expression of miRNA in addiction-related brain regions.Using bioinformatics analysis to locate candidate miRNA and predicted target molecules and identify candidate molecules.3.Real-time quantitative PCR was used to detect miRNA in plasma.Result1.A rat model of methamphetamine self-administration was established, which can simulate the behavioral characteristics of human drug addiction and lay a foundation for studying the neurobiological mechanism of methamphetamine addiction.2.Twelve and eight miRNA molecules were found in the dorsal striatum and prefrontal cortex of methamphetamine addicted rats with regular or obsessive-compulsive drug use characteristics, respectively.Bioinformatics analysis showed that the function of 11 differentially expressed miRNA and its target molecules such as miR-x6 might be related to methamphetamine addiction and neurotoxicity.3.Circulating miR-x18 was down-regulated in methamphetamine addicted rats with obsessive-compulsive drug use, while it was up-regulated in both circulatory miR-x19 groups.ConclusionTo sum up, a rat model of methamphetamine self-administration was established, in which 19 differentially expressed miRNA molecules were found in the dorsal striatum and prefrontal cortex of addictive animals.Two circulating miRNA molecules were found in plasma which may be differentially expressed, which provides clues for the study of the role of miRNA in methamphetamine addiction and the use of circulating miRNA as a biomarker for the diagnosis of methamphetamine addiction.
【学位授予单位】：中南大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R749.64

【共引文献】