电针调控胆碱能通路促进脑梗死大鼠运动功能重建的机制及量-效关系研究

It is the difficulty of clinical research to reconstruct the upper limb motor function after cerebral infarction. The key to improve the efficacy is to explore the neurobiological mechanisms of electro-acupuncture (EA) treatment of cerebral infarction, to reveal the dose-effect relationship of EA and to enhance synaptic plasticity. We have deduced quantitative relationship formula between EA "stimulation intensity" and EA frequency, current intensity and other parameters in the pre-clinical studies. The dose-effect and time-effect relationship in the process of promoting the reconstruction of cerebral infarction patients with upper limb motor function are clearly known. The project will be based on the Neurobiology technology as its essential research methods, taking into account a variety of cross-disciplinary technologies, as well as using the rat MCAO model as the focal cerebral infarction model. Then we will make some researches on dose-effect of different frequency EA, which can stimulate plasticity of synaptic structure and function, and promote the reconstruction of motor function. These researches are made by detecting index mark changes in behavior, endogenous acetylcholine levels and synaptic plasticity. And then the regalution of EA in rat model about the anti-inflammatory pathway mediated by M-, N-cholinergic receptor and the brain protection path will be dealt with.The present study was designed to explore the basis of endogenous substances, targets and mechanisms of EA treatment of cerebral infarction. Through this project, not only can we provide a scientific basis for revealing the internal mechanism of acupuncture to promote motor function after stroke reconstruction, but, more importantly, we will further enhance the efficacy of EA to promote reconstruction of motor function after cerebral infarction.

脑梗死后上肢运动功能的重建是临床研究的难点，探索电针治疗脑梗死的神经生物学机制，揭示电针治疗的量-效关系、提高突触可塑性是提高疗效的关键环节。申请者在前期研究中推导出电针"刺激量"与电针频率、电流强度等参数的数量关系公式，明确了电针促进脑梗死病人上肢运动功能的重建量-效、时-效关系。本项目将以神经生物学技术为核心研究手段，兼顾多种交叉学科技术，以大鼠MCAO模型为局灶性脑梗死模型，通过检测行为学、内源性乙酰胆碱含量及突触可塑性标志性指标的变化，对不同频率电针激发突触结构与功能可塑性、促进运动功能重建的量效关系进行研究；进而探讨电针对模型大鼠M型、N型胆碱能受体介导的抗炎通路、脑保护通路的调控作用，旨在揭示电针治疗脑梗死的内源性物质基础、作用靶点和机制。通过本项目实施，不仅可以为揭示电针促进脑卒中后运动功能重建的内在机制提供科学依据。更重要的是将进一步提高电针促进脑梗死后运动功能重建的疗效。

脑梗死后上肢运动功能的重建是临床研究的难点，探索电针治疗脑梗死的神经生物学机制，揭示电针治疗的量-效关系、提高突触可塑性是提高疗效的关键环节。申请者在前期研究中推导出电针“刺激量”与电针频率、电流强度等参数的数量关系公式，明确了电针促进脑梗死病人上肢运动功能的重建量-效、时-效关系。本项目将以神经生物学技术为核心研究手段，兼顾多种交叉学科技术，以大鼠MCAO模型为局灶性脑梗死模型，通过检测行为学、内源性乙酰胆碱含量及突触可塑性标志性指标的变化，对不同频率电针激发突触结构与功能可塑性、促进运动功能重建的量效关系进行研究；进而探讨电针对模型大鼠M型、N型胆碱能受体介导的抗炎通路、脑保护通路的调控作用，旨在揭示电针治疗脑梗死的内源性物质基础、作用靶点和机制。.本项目研究结果显示：1.电针在抗脑缺血作用中存在量-效关系；不同频率电针对突触可塑性影响存在差异，突触可塑性是量-效关系产生的基础。50 Hz电针存在最佳的量-效关系。.2.Ach的代谢参与了脑梗死后运动功能重建的过程，电针在抗脑缺血过程中同时调控了M型、N型胆碱能受体介导的抗炎通路、脑保护通路。不同频率电针激活的胆碱能通路并不相同：50Hz电针产生最佳量-效关系的关键环节是在三个水平均显著的、同等程度的激活了抗炎通路和脑保护通路。.3.50Hz电针能存在最佳量-效关系的作用靶点之一是在抗脑缺血保护过程中，同时、无差别的影响M受体介导的抗炎通路和N受体介导的脑保护通路。.4.电针可能通过调控内源性物质Ach的代谢与信号转导通路、激发突触功能和结构发生可塑性变化，促进脑梗死后运动功能重建。.通过本项目实施，不仅可以为揭示电针促进脑卒中后运动功能重建的内在机制提供科学依据。更重要的是将进一步提高电针促进脑梗死后运动功能重建的疗效。