兴奋性氨基酸受体拮抗剂减轻宫内窘迫诱发的新生鼠Tau蛋白的过度磷酸化和认知障碍

发布时间：2018-05-17 16:28

本文选题：Tau蛋白 + 认知功能　；参考：《中国现代医学杂志》2015年26期

【摘要】：目的通过观察兴奋性氨基酸受体拮抗剂对宫内窘迫后新生鼠认知能力和Tau蛋白过度磷酸化的影响,探讨兴奋性氨基酸受体拮抗剂对Tau蛋白过度磷酸化的调节及两者对新生鼠认知能力的影响。方法采用析因设计,将每只大鼠视为1个单位,予2个处理因素,即宫内窘迫处置和否(2水平:无处置,施行宫内窘迫,即夹闭孕鼠的子宫动脉2/3持续10 min)和兴奋性氨基酸受体拮抗剂使用和否[3水平:注射生理盐水N-甲基-D-天冬氨酸(NMDA)受体拮抗剂MK-801、黄芪总苷]的所有组合。全部宫内窘迫处置结束后母鼠继续妊娠至新生鼠娩出,待新生鼠生长至12周时开始Morris水迷宫(MWM)检测认知能力后留取海马。HPLC法检测谷氨酸(Glu)在海马内的浓度;免疫组织化学SP法检测Tau蛋白5(总Tau蛋白)以及磷酸化Tau蛋白pPHF1Ser396/404、p-AT8Ser199/202、p-12E8Ser262在海马中的表达水平。结果宫内窘迫和Glu受体拮抗剂造成大鼠学习和记忆等脑功能障碍,即延长受试者的逃避潜伏期(EL),缩短受试者的空间探索时间(SET),两干预因素的影响结果呈现相减的效果。宫内窘迫可增加海马中Glu的浓度;Glu受体拮抗剂对海马内的Glu浓度无显著的影响。宫内窘迫和Glu受体拮抗剂对海马总Tau蛋白表达无影响。宫内窘迫可增加海马中磷酸化Tau蛋白的表达;Glu受体拮抗剂可缓解海马Tau蛋白的过度磷酸化程度;两者叠加的影响可以呈现相减的效果。结论 Glu受体的拮抗剂和黄芪总苷可以缓解宫内窘迫诱发的缺血缺氧强应激后的神经元损伤,其具体机制与阻断兴奋性毒性和缓解海马内Tau蛋白的过度磷酸化程度有关。
[Abstract]:Objective to investigate the effect of excitatory amino acid receptor antagonist on cognitive ability and Tau protein overphosphorylation in neonatal rats after intrauterine distress, and to explore the effect of excitatory amino acid receptor antagonist on the overphosphorylation of Tau protein and their effects on cognitive ability of neonatal rats. Methods the factorial design was used to treat each rat as 1 single ones. Position, 2 treatment factors, namely, the treatment of intrauterine distress (2 levels: no disposal, intrauterine distress, uterine artery 2/3 persistent 10 min) and [3 levels of excitatory amino acid receptor antagonists: N- methyl -D- aspartate (NMDA) receptor antagonist MK-801, all combinations of Astragalus membranaceus total glucoside. Morris water maze (MWM) was used to detect the concentration of glutamic acid (Glu) in the hippocampus after the Morris water maze (MWM) detected the cognitive ability of the newborn rats after the growth of the newborn rats to 12 weeks. The immunohistochemical SP method was used to detect the Tau protein 5 (total Tau protein) and the phosphorylated Tau protein pPHF1Ser396/404, p-AT8Se. The expression level of r199/202, p-12E8Ser262 in the hippocampus. Results intrauterine distress and Glu receptor antagonists cause brain dysfunction such as learning and memory in rats, that is, prolonging the escape latency (EL) of the subjects and shortening the space exploration time (SET) of the subjects (SET). The effects of the two intervention factors are reduced. The concentration of Glu, Glu receptor antagonist had no significant effect on the Glu concentration in the hippocampus. Intrauterine distress and Glu receptor antagonists had no effect on the expression of total Tau protein in the hippocampus. Intrauterine distress could increase the expression of phosphorylated Tau protein in the hippocampus; the Glu receptor antagonist could alleviate the degree of excessive phosphorylation of hippocampal Tau protein; the effect of both superposition can be presented. Conclusion Glu receptor antagonist and Astragalus membranaceus glycoside can alleviate the injury of neurons after the severe stress induced by hypoxia and hypoxia induced by intrauterine distress. The specific mechanism is related to blocking the excitotoxicity and alleviating the degree of excessive phosphorylation of Tau protein in the hippocampus.
【作者单位】：解放军第452医院麻醉科;解放军第452医院医学工程科;解放军第452医院眼科;天津市胸科医院心内科;
【基金】：中国博士后科学基金面上项目(No:2013M530880)
【分类号】：R714

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