基于HPA轴调控和海马核受体MR、GR功能改变探讨HCMV宫内感染致学习记忆损伤的机制

项目名称： 基于HPA轴调控和海马核受体MR、GR功能改变探讨HCMV宫内感染致学习记忆损伤的机制

项目编号： No.81472167

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 吴德

作者单位： 安徽医科大学

项目金额： 72万元

中文摘要： 儿童智力障碍是发病率极高，且缺乏有效治疗手段的一组严重神经残疾。课题组前期以智力障碍的首要病因（宫内感染）为突破点，成功建立了HCMV宫内感染SD大鼠模型，追踪研究发现子代大鼠的智力障碍缓慢加重，推测海马损伤诱发的HPA轴调节紊乱是其主要机制。本研究拟通过免疫荧光双标、共聚焦激光扫描术、RT-PCR与放射性同位素原位杂交等，系统研究HCMV宫内感染对海马-HPA轴结构和功能发育的影响；应用DXM、RU486和R121919等实验抑制或阻断HPA轴调节模式，探讨感染导致的HPA轴紊乱的机制；应用全导神经电生理仪检测海马各区的LTP/LTD改变，明确突触可塑性影响的程度和范围。以海马损伤和HPA轴功能紊乱的互相影响为切入点，结合海马核受体（MR、GR）功能异常和突触可塑性的损伤，阐明HCMV宫内感染致子代智力障碍逐步加重的病理生理机制，为临床预防和治疗儿童智力残疾提供新的思路和药物治疗靶点。

中文关键词： 智力残疾；人巨细胞病毒；学习记忆；丘脑-垂体-肾上腺轴；损伤

英文摘要： As a group of severe neurologic disability, incidence of children's intelligence disability is high and lack of effective treatments. We selected intrauterine infection as the breakthrough point and have successfully established a SD rat model of HCMV congential infection in central nervous system. Preivous research found that functions of learning and memory and hippocampal structure of pups in the model are progressive. Here，we speculates that HPA axis dysfunction and abnormal expression of hippocampal MR and GR may is the main pathophysiological mechanism of this phenomenon. The change of hippocampal-HPA axis function and structure development influenced by HCMV intrauterine infection in a systematic would be studied by double immunofluorescence, confocal laser scanning, RT-PCR and radioactive isotopic in situ hybridization. The mechanims of HPA axis dysfunction would be detected by Dexamethasone stimulation test, RU486 and R121919 blocking tests. LTP / LTD in all area of hippocampus would be measured by whole-mediated neural electronphysiological instrument. To elaborate the role of imbalanced regulation of HPA axis in the impairment of leaning and memory by HCMV intrauterine infection, the functional changes of the receptors( MR and GR) in hippocampus, damage of hippocampal synaptic plasticity and the results of neurobehavioral testing would be comprehensively analyzed. The results may provide spiritual insight of clinical prevention and a new therapeutic target for children with intelligence disability.

英文关键词： Intellectual disability;Human cytomegalovirus;Learning and memory;Hypothalamic pituitary adrenal axis;Injury