【作者】 姜婉贞；

【导师】 战丽彬；

【作者基本信息】 大连医科大学 ， 中西医结合临床， 2006， 硕士

【摘要】 目的:突触是神经元间进行信号传递的重要结构,它的破坏和丢失对神经系统的机能将产生重大影响。突触功能障碍及缺失是发生于阿尔茨海默病(Alzheimer’s disease, AD)早期的病理过程,是AD疾病过程中的重要神经病理改变之一,并且是与认知功能下降最为密切的病理表现。树突棘是存在于哺乳动物大脑神经元树突干上的小突起,它构成中枢神经系统兴奋性突触传递的原始位点,是学习和记忆活动的生物学基础。在AD病人脑中,发现有树突棘丢失及密度的减少,树突退化等现象。树突棘内含有多种细胞表面受体、肌动蛋白细胞骨架、脚手架蛋白等多种成分,它们对树突棘的生长发育成熟以及结构的稳定起调节作用。其中以树突棘相关的Rap-特异性GTPase-活化蛋白(spine-associated Rap guanosine triphosphatase (GTPase) activating protein, SPAR)为代表,它与树突棘成熟及形态的维持密切相关。在神经元活化时SPAR可被血清诱导激酶(serum-inducible kinase, SNK)降解,从而导致树突棘结构的失稳定。本课题组既往研究表明,滋补脾阴方药(Zi-Bu-Pi-Yin decoction, ZBPY)具有抗氧化及改善衰老个体学习记忆能力,具有显著的神经保护作用。因此探讨滋补脾阴方药的神经保护作用与维持树突棘结构和功能之间的相关性及其分子机制,对于防治AD及相关的以进行性脑功能障碍为特点的神经退行性疾病是有重要意义的。本实验目的在于观察滋补脾阴方药预处理对于谷氨酸引起的原代培养的大鼠海马神经元树突棘形态结构损伤的保护作用,探讨滋补脾阴方药对于树突棘内与其形态结构稳定密切相关的SNK-SPAR途径的调节作用,从而深入探讨其相应的神经保护作用及其与树突棘形态调节之间更多还原

【Abstract】 Synapse is the important structure for transmission between neurons. The dysfunction and loss of synapse will destroy the function of nervous system greatly. Synapse loss is one of the most important pathological changes of Alzheimer’s disease (AD). Synaptic dysfunction and failure are processes that occur early in AD, it is the best current pathologic correlate of cognitive decline. Dendritic spines are some small protrusions from the dendrites of the principal neurons in mammalian. Dendritic spines represent the postsynaptic component of most excitatory synapses. Spines are the main sites of excitatory synaptic transmission in central nervous system. Synaptic transmission is thought to be the physiological basis of learning and memory. Hundreds of molecules have been identified in the PSD: receptors, cytoskeletal proteins, scaffolding proteins, and signal proteins who are in charge of the density and shape of dendritic spines. Spine-associated Rap guanosine triphosphatase (GTPase) activating protein (SPAR) is an important candidate for mediating activity-dependent remodeling of synapses. And is critically involved in spine maturity, especially in the mature spine formation and the maintenance of spine maturity. Serum-inducible kinase (SNK), one of the polo-like kinases, induced by synaptic activity and was targeted to dendritic spines, eliminates SPAR protein, and causes loss of mature dendritic spines and synapses. The previous studies of our group suggested that Zi-Bu-Pi-Yin decoction (ZBPY) has notable functions of against aging such as anti-oxidation, improve the ability of study and memory. Therefore we want to make it clear that the molecular mechanism of ZBPY for preserving the structure and function of synapses, especially the更多还原