基于代谢组学的地黄饮子对双转基因痴呆小鼠生物标志物的影响

With the acceleration of the aging process,Alzheimer's disease (AD) incidence is increasing, because of its complex pathogenesis, lack of treatment methods , how to control has become an international problem.Dihuangyinzi Department of ancient classical prescription, Widely used in the treatment of a variety of neurological diseases, such as dementia, stroke, Parkinson, etc.The preliminary study of the research group shows that the prescription has anti-aging, improve learning and memory, regulate the apoptosis of nerve cells, promote the conduction of nerve signals and protect the structure and function of the nervous system.This project is based on previous studies, using biomarkers as the starting point, Study on the changes of AD specific marker metabolites by metabonomics,to evaluate the effect of effective compound on different stages of AD model,to explore its mechanism of action. To provide a scientific basis for the study of Dihuangyinzi for Alzheimer's disease and clinical application,and lay the foundation for the development of local drug prevention and treatment of AD.Influence study method for the first time application of metabolomics on the metabolic profile of Dihuangyinzi prevention of double transgenic mouse model of dementia and biomarkers.To explore the mechanism of multi-target Dihuangyinzi intervention AD,To reveal treatment of the ancient classical prescription on the changes of metabolic processes in chronic diseases with complex clinical and pathogenic mechanism has important theoretical significance and application value.

随着人类老龄化进程的加快，阿尔兹海默病（AD）的发病率日益增高，因其发病机制复杂，治疗方法欠缺，如何防治已成为国际性难题。地黄饮子系古代名方，临床上广泛用于治疗多种神经系统疾病，如痴呆，中风，帕金森等。课题组前期研究表明，该方具有抗衰老,改善学习记忆，调控神经细胞凋亡，促进神经信号的传导和保护神经系统的结构及功能。本项目在以往研究的基础上，以生物标记物为切入点，利用代谢组学方法探寻AD特异标志性代谢产物的改变，评价有效复方对AD模型不同阶段的干预作用，研究其作用机制，为地黄饮子防治老年性痴呆的研究和临床应用提供科学依据，并为防治AD的古方新药开发奠定基础。课题系首次应用代谢组学的研究方法对地黄饮子防治双转基因痴呆模型小鼠的代谢轮廓及生物标记物的影响，探寻地黄饮子干预AD的多靶点作用机制，揭示古代经典名方防治临床复杂发病机制的慢性疾病代谢过程变化，具有重要的理论意义和应用价值。

阿尔茨海默病（Alzheimer’s disease，AD）是一种以记忆能力减退、认知功能障碍、行为异常为临床特征的神经退行性疾病。AD缓慢起病，逐渐加重，其发病机制仍不清楚，目前尚缺乏有效的治疗方法。中医学理论认为肾虚痰阻是AD的重要病机，地黄饮子具有补肾化痰开窍之功，符合这一病机。本研究采用国际公认的双转基因痴呆症模型小鼠，从行为学、脑组织病理学、代谢组学等方面，观察了地黄饮子防治AD的疗效和作用机制。结果显示地黄饮子可提高AD模型小鼠学习记忆能力，保护小鼠病变脑组织。对给药第一、第二、第三个月APP/PS1小鼠脑组织、尿液代谢组学检测，显示地黄饮子可以通过多靶点防治AD，并确定了其特异标志性代谢产物。