HDAC2调控NR2B/HGN表达在孕早期母体接受氯胺酮麻醉致大鼠子代学习记忆损害中的作用

项目名称： HDAC2调控NR2B/HGN表达在孕早期母体接受氯胺酮麻醉致大鼠子代学习记忆损害中的作用

项目编号： No.81460175

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 罗佛全

作者单位： 南昌大学

项目金额： 47万元

中文摘要： 正负调控平衡在学习记忆中的作用已得到重视。NR2B和HGN是海马内重要的正、负调控因子。课题组2013年结题的国家自然科学基金课题研究发现，孕早期母体接受氯胺酮麻醉通过抑制NR2B表达、促进HGN表达损害子代学习记忆，但其上游机制尚不清楚。HDAC2是调控学习记忆的上游因子，通过HDAC2-CREB-NR2B通路影响学习记忆，但其在氯胺酮对子代学习记忆损害中的作用不清楚。本项目拟分析孕早期母体接受氯胺酮麻醉后，SD大鼠子代海马HDAC2表达及活性变化与磷酸化CREB表达水平、NR2B/HGN表达平衡的关联及其与学习记忆的关系，以证实孕早期母体接受氯胺酮麻醉是否通过HDAC2-CREB-NR2B通路破坏子代大鼠海马区NR2B/HGN表达平衡，从而损害子代学习记忆功能，并用NR2B、HDAC2抑制剂、HGN反义核苷酸及HDAC2基因敲除大鼠模型进一步证实。对临床麻醉选择有重要意义。

中文关键词： 组蛋白去乙酰化酶2；N-甲基-D-天冬氨酸受体2B亚单位/hippyragranin；子代；氯胺酮；学习记忆

英文摘要： The critical role of the expression balance between possitive and negative regulating factors in the formation and maintenance of learning and memory function has been well recognized.N-methyl-D-Aspartate receptor 2B unit (NR2B) and hippyragranin (HGN) are the established positive and negative regulating factors of learning and memory function in the hippocampus.Our preliminary study of national natural science fund project (81060093) showed that maternal ketamine anesthesia during early gestation could impair the learning and memory function of offspring rats' through down-regulating the expression of NR2B while up-regulating the expression of HGN.But role of the change of the expression balance of NR2B and HGN in the pathogenesis and it's upstream mechanism is still not known yet.It is known that histone deacetylase 2 (HDAC2) upstream regulating factors of learning and memory function by the pathway HDAC2-cyclic adenosine monophosphate response element binding protein (CREB)-NR2B,while it's role in the pathogenesis of learning and memory function impairment of the offspring rats' induce by ketamine anesthesia during the early gestation is not known yet.In present study,both of the changes of the expression levels and activity of HDAC2 in the hippocampus and their relationship to the expression levels of CREB,NR2B,HGN and learning and memory function of the offspring rats' with maternal ketamine exposure during early gestation will be researched.Thus to clarify whether ketamine anesthesia during early gestation impair the learning and memory function by disturbing the expression balance between NR2B and HGN through the pathway HDAC2-NR2B-CREB.Then,the inhibitors of NR2B and HDAC2,HGN antisense and HDAC2 gene knockout rats will be used to prove it further.It is critical to the clinical anesthesia selection.

英文关键词： histone deacetylase 2 (HDAC2);N-methyl-D-Aspartate receptor 2B unit (NR2B)/hippyragranin (HGN);offspring;ketamine;learning and memory function