解毒通络治法调整脑内微环境改善AD失连接的临床基础研究

Research on brain disconnection in Alzheimer's disease is now one of the focal issues in this field. More and more researchers indicated a common viewpoint that the disorders of microenvironment among neurons, axons and neuroglia cells are the core pathogenesis of brain disconnection of AD. From the traditional Chinese medical (TCM) perspective, these disorders are directly due to DUSUNNAOLUO, a TCM symptom and, correspondingly, JIEDUTONGLUO is the approach to crack this hard nut. However, studies about the Curative principles and therapeutic methods on this core pathogenesis ,as well as the evaluation of its correspondent therapy, are very few and far behind. To prove this pathology assumption, we adopt multi-modality imaging technique(fMRI, sMRI , DTI, and PET) and longitudinally investigate the mild AD progression about brain disconnection, microenvironment and energy metabolism before and after our pharmacological treatment, so as to observe the change of microenvironment in those important disconnection-related brain regions and the relationship between their energy metabolism and signal transduction. Furthermore, we also designed animal experiments to inspect the microscopic effect of this oriental therapy in Myelin integrity, Synaptic connections and mitochondria’s function. Finally, a structural-functional brain network model will be made up and a behavioral-metabolic-chemical assessment system as a key core technology will be accomplished to give this therapy a scientifical and systematical evaluation . Our studies will not only validate a new and available method for AD treatment, but also the studies have great value to investigate pathological mechanism for AD...

阿尔茨海默病患者（Alzheimer's disease, AD）脑区“失连接”模式的解读和机制探讨，是当今AD研究领域的焦点问题。越来越多的科学家认为神经元-胶质细胞-轴突间微环境紊乱是这种连接中断的核心病机，而 “毒损脑络”正是导致其病机的关键。然而，围绕其核心病机的相关治则治法及疗效评估却远远滞后。本项目拟通过多模态神经影像技术（fMRI，sMRI和DTI）及正电子发光断层扫描PET成像，观察解毒通络治法对轻度AD患者干预前后，脑内失连接关键脑区微环境改变及能量代谢间的关联；通过动物实验研究，在微观层次验证和解析人脑失连接关键区域的髓鞘完整性、突触连结、线粒体功能活动及相关分子机制；通过不同算法建立人脑功能网络和解剖结构网络模型，关联认知行为和能量代谢相关指标，集成药物评估的关键核心技术。本项目不仅拓展了“毒损脑络”理论应用于痴呆治疗的新途径，而且在探索AD的病理机制方面具有重要意义

阿尔茨海默病患者（Alzheimer's disease, AD）脑区“失连接”模式的解读和机制探讨，是当今AD研究领域的焦点问题。神经元-胶质细胞-轴突间微环境紊乱是这种连接中断的核心病机，“毒损脑络”正是导致其病机的关键。然而，围绕该病机的解毒通络治法及疗效评估却远远滞后。项目完成了解毒通络治法干预轻中度AD患者的疗效评价、认知功能评估及血液生化指标检测。采用多模态神经影像技术（fMRI，sMRI和DTI）及正电子发光断层扫描（PET）成像技术阐明了老年性痴呆疾病风险的脑失连接机制和解毒通络治法改善轻度认知功能障碍患者认知功能的脑神经机制，对中药药效的客观临床评价具有借鉴意义。应用不同算法建立了人脑功能网络和解剖结构网络模型，关联了认知行为和脑区激活、能量代谢相关指标。研究揭示了APOE基因启动子rs405509多态性加速认知老化的灰质结构失连接神经机制。同时，完成了解毒通络中药改善AD动物模型学习记忆能力的疗效评价及其分子机制研究，揭示了解毒通络治法改善认知功能障碍的脑神经机制。通过以上临床和动物实验研究，建立了药物评估的关键核心技术。本项目不仅拓展了“毒损脑络”理论应用于痴呆治疗的新途径，而且在探索AD的病理机制方面具有重要意义。