中文摘要
阿尔海默病(AD)是一种常见的老年性神经退行性疾病,伴随人口老龄化,其发病率和死亡率逐年增加,但仍缺乏有效疗法。本项目建立在针刺治疗AD临床有效,并经多年实验研究有所发现基础之上。我们前期研究发现针刺对SAMP8神经树突受损及RhoA/ROCK通路的相关因子失衡有良性调节作用,从而提出“针刺通过调节RhoA/ROCK通路改善痴呆模型鼠海马突触可塑性”的工作假说。课题以痴呆模型鼠SAMP8为研究对象,以海马突触可塑性为切入点,以调控突触可塑性的RhoA/ROCK信号通路为主线,应用在体LTP、高尔基染色、qPCR和Western等技术观测海马突触可塑性相关指标(LTP、树突棘形态和密度)的改变和RhoA/ROCK通路中相关因子(RhoA、ROCKⅡ、MLC2、LIMK2和CRAMP2)表达和活性的变化,以及针刺干预效应,探讨针刺防治AD的机制,为针刺AD的临床应用和推广提供实验依据。
英文摘要
Alzheimer's disease (AD) is one of neurodegenerative diseases in the elderly people, and its incidence and mortality is increasing with the aging of the population rencently, but an effective cure is still lack. The project builds on the clinically effects of acupuncture on AD and the experimental research progression in the past years. Preliminary studies showed acupuncture had played a benign regulatory role of damaged dendrites and RhoA/ROCK pathway imbalance by neuropathology and proteomics. Thus, the working hypothesis is generated that acupuncture may improve hippocampal synaptic plasticity of dementia model mouse by regulating RhoA/ROCK signaling pathway. SAMP8 is the subject of this study, and hippocampal synaptic plasticity is a suitable solution. RhoA/ROCK signaling pathway which regulates synaptic plasticity is the cardinal line. LTP in vivo, Golgi staining, qPCR and Western techniques will be used, hippocampal synaptic plasticity related parameters (LTP, dendritic spine morphology and density) and the expression and activity of RhoA/ROCK pathway-related factors (RhoA, ROCKⅡ, MLC2, LIMK2 and CRAMP2) will be detected. Intervention effects of acupuncture on these indicators will be evaluated. So that we can explore the mechanism of acupuncture prevention of dementia and provide experimental evidence for acupuncture clinical application and generalization.
