文章摘要
刘颖异 胡玲芹 张映 李方钦 王静 潘玉君.PSD-95 与脑缺血的关系及其调控机制研究[J].,2014,14(9):1796-1800
PSD-95 与脑缺血的关系及其调控机制研究
The Study on the Relationship Between PSD-95 andCerebral Ischemia and their Regulation Mechanisms
  
DOI:
中文关键词: 突触后密度蛋白-95  脑缺血  N-甲基-D-天冬氨酸盐受体
英文关键词: PSD-95  Cerebral ischemia  NMDAR
基金项目:黑龙江省教育厅海外学人科研资助项目(1155h005);哈尔滨医科大学附属第一医院科研基金(R08-002)
作者单位
刘颖异 胡玲芹 张映 李方钦 王静 潘玉君 哈尔滨医科大学附属第一医院神经内科 
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中文摘要:
      PSD-95(突触后密度蛋白-95)在突触后密度区含量丰富,具有复杂的结构域,与膜受体、离子通道、细胞粘附因子和信号分子 等相互作用聚集成大分子复合物,在突触的可塑性、学习记忆、大脑的病理生理紊乱等起重要作用。PSD-95 与脑缺血神经元损伤 和凋亡的分子机制有密切联系。脑缺血再灌注后PSD-95 在缺血侧皮层的变化表现为PSD-95 阳性细胞数的减少和细胞形态的受 损改变。抑制NMDA 受体活性的治疗策略包括破坏受体本身、钙离子通道阻滞剂、破坏PSD-95/NMDAR 相互作用、破坏 PSD-95/nNOS相互作用、nNOS抑制剂药物干预。已有研究发现在大鼠大脑中动脉栓塞模型中抑制PSD-95 复合体之间的相互作 用可以改善脑缺血。实验性的PSD-95 抑制剂减少了短时间和长时间局部脑缺血大鼠的梗死面积、并恢复相应的运动功能治疗脑 缺血。本文重点研究PSD-95 与脑缺血的关系及其调控机制。
英文摘要:
      PSD-95 (postsynaptic density protein-95) which is abundant in postsynaptic density area has complex domains. It interacts with membrane receptors,ion channels, cell adhesion molecules, as well as with signal molecules, gathering into large molecular complexes and playing an important role in synaptic plasticity, learning and memory, pathophysiological disorders of brain. PSD-95 has closely connection with molecular mechanism of cerebral ischemia neuronal injury and apoptosis. Cerebral ischemia cortical shows PSD-95 positive cell number decrease and cellular morphology damage after cerebral ischemia-reperfusion. Therapeutic strategies to dampen NMDAR activity include disruption of the receptor itself, Ca2+ blockers,disruption of the NMDAR/PSD-95 interaction, disruption of the PSD-95/nNOS interface,Pharmacological intervention with nNOS inhibitors. It is studied that to inhibit the interaction with PSD-95 complex can ameliorate cerebral ischemia in the middle cerebral artery occlusion (MCAO) mode of rat. Experimental PSD-95 inhibitors reduce the infarct size which is made by transient and permanent focal ischemia in the rat, then recover the corresponding motion function to treat cerebral ischemia. The article mainly studies the relationship of PSD-95 and cerebral ischemia as well as their regulation mechanisms.
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