阿尔茨海默病与帕金森病共性证候要素的电化学机制研究

Our Previous NSFC funded project proposed the hypothesis that Alzheimer's disease(AD) and Parkinson's disease(PD) share the common syndrome.On the view of neuronal apoptosis, we studied the crosstalk effect between the main excitatory and inhibitory neurotransmitter in the brain, which exist properties of Yin and Yang.Based on the theory of Yin and Yang in equilibrium or unequilibrium are the understanding of health and disease in traditional Chinese medicine, and the biological phenomena that both LTP-LTD and Glutamate-GABA exist properties of Yin and Yang,we further put forward a new hypothesis that brain's electrochemical signal in unequibibrium is the biological mechanism of AD's and PD's common syndrome factor through introducing the theory of syndrome factor to exprimental design. From the common understanding of AD and PD in Chinese and Western medicine,we pay close attention to the advancements of Brain Science that have the scientific connotations of Chinese medicine.The study would be developed from the levels of molecular and cellular experiment, neuronal network experiment and animal experiment. The main object is to attempt to elucidate the scientific mechanism of "the syndrome of deficiency of kidney-essence and empty of brain marrow",which is recognized as the common syndrome factor of AD and PD.This study would provide experimental foundation to the theory of preventing and curing AD and PD using Chinese medicine, also render an innovative try to guide experimental research by the theorical thinking of Chinese medicine.

申请人主持的前项NSFC课题提出阿尔茨海默病(AD)和帕金森病(PD)异病同证的假说，并从神经元凋亡机制出发，对具有阴阳属性的兴奋和抑制类神经递质的交互作用开展研究。本项目基于阴平阳秘和阴阳失衡是中医学对健康和疾病的理论认识，结合LTP-LTD与谷氨酸-GABA是具有阴阳属性的脑电机制和神经递质的生物学现象，将证候要素提取理论引入实验设计中，提出脑电化学信号阴阳失衡是AD和PD共性证候要素生物学机制的假说，拟从中西医学对AD和PD的共性认识出发，着眼于具有中医理论科学内涵的现代脑科学研究进展，在分子水平，细胞水平，神经网络水平以及整体动物水平开展研究，试图阐明AD和PD的共性证候要素- - "肾精虚-脑髓空"的现代科学机制，为中医药防治脑老化疾病的异病同证理论提供实验依据，也为应用中医理论思维指导实验研究提供创新性尝试。

本研究将证候要素提取理论引入实验设计中，提出脑电化学信号阴阳失衡是 AD 和 PD 共性证候要素生物学机制的假说，对具有阴阳属性的兴奋和抑制类神经递质的交互作用开展研究。在体实验：首先采用脑室注射冈田酸（OKA）所引起的学习记忆障碍拟AD动物模型，采用Morris水迷宫对模型进行评价，并以Rg1作为阳性对照药物进行验证。进而采用APP/PS1转基因动物模型模拟阿尔茨海默病，过表达人A53Tα-synuclein小鼠模拟帕金森病，对上述不同年龄段的转基因小鼠的学习记忆能力变化开展了研究。结果表明，神经退行性疾病的发生与年龄变化（肾中精气生理性变化）密切相关，为“肾精亏，脑髓空”提供了科学的理论依据。体外实验：构建星形胶质细胞损伤的体外模型，对星形胶质细胞和神经细胞进行共培养，研究星形胶质细胞活化后对神经元释放神经递质谷氨酸及γ氨基丁酸的影响作用，探讨基于缝隙连接蛋白CX43的阿尔茨海默病和帕金森病病共性机制研究。结果表明星形胶质细胞活化后可对γ氨基丁酸的释放产生影响，并且其CX43蛋白表达呈增加趋势。