基于对NogoA-NgR/Rho-ROCK通路调节的清脑益智方促神经元突触重塑治疗VD的机制研究

项目名称： 基于对NogoA-NgR/Rho-ROCK通路调节的清脑益智方促神经元突触重塑治疗VD的机制研究

项目编号： No.81202653

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学八处

项目作者： 秦秀德

作者单位： 天津中医药大学

项目金额： 23万元

中文摘要： 神经元突触重塑是目前包括血管性痴呆在内的神经退行性疾病的研究前沿，清脑益智方是基于血管性痴呆"毒损脑络"的病机理论制定的治疗血管性痴呆有效的临床经验方，前期的临床研究证明其有改善VD患者认知的作用，但它是否可通过调节NogoA-NgR/Rho-ROCK信号通路影响神经元突触重塑而起作用，目前尚无相关研究。本研究采用大鼠血管性痴呆模型和神经元细胞缺氧复氧损伤模型，运用免疫组化、RT-PCR、Western blot、电镜形态学观察及透射电镜超微结构观测等技术，研究清脑益智方对拟血管性痴呆大鼠皮层和海马区神经元突触结构的影响，及清脑益智方含药脑脊液对缺氧复氧损伤皮层神经元细胞NogoA-NgR/Rho-ROCK信号转导通路的调控作用及对神经元细胞突触重塑的影响。通过探讨清脑益智方对神经元突触重塑的作用，并阐释其治疗血管性痴呆的部分机制，为临床用药提供科学依据。

中文关键词： 清脑益智方；血管性痴呆；神经元；突触重塑；凋亡

英文摘要： Synaptic remodeling is the research fronts of neurodegenerative diseases including vascular dementia. Qingnao Yizhi fomula is based on the vascular dementia's pathology theory "poison injures brain collaterals",clinical trial has proved that Qingnao Yizhi fomula could ameliorate the cognitive function of vascular dementia patients,there are already some subjects which studied the formula 's possible therapeutical mechanism,but there is still no research which is based on investigating the fomula's effect on neuronal synaptic remodeling based on regulating the signaling pathway of NogoA-NgR/Rho-ROCK.This subject applies the 2-VO rat vascular dementia model and hypoxia-reoxgenation cortical neuron cell,through using the methods or equipments of immunohistochemistry、RT-PCR、Western blot、electron microscope and transmission electron microscope、etc,study the Qingnao Yizhi fomula's affecting effect on the neuronal synaptic remodeling of the vascular dementia mouse's cerebral cortex and hippocampus area,and the regulating effect of cerebrospinal fluid containing Qingnao Yizhi fomula on the signaling transduction passway of NogoA-NgR/Rho-ROCK,as well as cerebrospinal fluid containing Qingnao Yizhi fomula's effect on the synapse shape and structure of the hypoxia-reoxgenation cortical neuron cell. Through studying the Qi

英文关键词： QingnaoYizhi fomula；vascular dementia；neuron；synaptic plasticity；apoptosis