【作者】 成威；

【导师】 李友元；

【作者基本信息】 中南大学 ， 老年医学， 2008， 硕士

【摘要】 阿尔茨海默病(AD)是一种中枢神经系统退行性变性的疾病,以认知记忆功能受损、行为异常、人格改变为临床表现;以大脑组织中神经纤维缠结、β-淀粉样蛋白沉积,神经元变性凋亡,神经髓鞘松解、血管淀粉样变等为病理特征。AD的患病率随着人口老龄化逐年升高,已成为严重影响人们生存期和生活质量的重要因素。因此,关于痴呆的研究有着非常重要的实际意义。AD的病因尚未明确,治疗也在不断的探索中,作为“常服有延年益寿的作用”的祖国传统中药黄精,其提取液——黄精多糖(PP)具有抗衰老、增强免疫力等作用。本实验采用不同浓度黄精多糖溶液对APP转基因小鼠灌胃干预,观察黄精多糖对APP转基因小鼠学习记忆能力及其对大脑海马超微结构的影响。探讨黄精多糖对实验性AD的作用机制,以寻求防治疗老年痴呆的新的途径和方法。目的:探讨黄精多糖对实验性AD的疗效及其作用机理。方法:以APP转基因小鼠作为研究对象,用不同浓度的黄精多糖溶液连续灌胃45天。采用Morris水迷宫法测试小鼠的主动学习记忆能力;采用透射电镜观察海马超微结构并对其进行体视学分析和统计学方法的分析。结果:实验结果表明黄精多糖具有以下作用:1.行为学:治疗组(LDG与HDG)与对照组相比,潜伏期缩短、跨越平台的次数增多,错误次数减少(p＜0.01);不同剂量治疗组之间在潜伏期、跨越平台次数之间也有统计学意义(p＜0.05)2.海马超微结构:与空白对照组相比:(1).黄精多糖治疗组神经元数目相对较多,变性程度减轻,与黄精多糖治疗剂量相关。(2).治疗组小鼠脑组织水肿、细胞器空泡样变性明显减少(p＜0.01)。(3).治疗组有关线粒体、突触及突触界面结构的体视学参数有明显改善(p＜0.05)。结论:黄精多糖能改善APP转基因小鼠中枢神经系统超微结构及维护中枢神经系统微环境稳定,减少氧化损伤及炎症反应,保护中枢胆碱能系统,显著改善其学习记忆能力,且具有一定的量效关系。黄精多糖是治疗实验性AD的有效药物。更多还原

【Abstract】 Alzheimer’s disease (AD) is the degeneration of the central nervous system (CNS). It’s clinically characterized by impairment of memory & cognition, disordered behavior and changed personality, while Neurofibrillary tangles (NFT) ,βAmyloid protein deposition, Neuronal degeneration or apoptosis, neural sheath solution and vascular amyloidosis in brain tissue are its pathological features. With the aging of the population, AD has become one of the most severe problems, which threaten people’s life span and quality of life. So it is of great practical value for us to study the disease.The cause of AD is unknown, and the treatment of it is still in the process of exploring. Polygona-Polysaccharose (PP) is extracted from Rhizoma Polygonati, which is a traditional Chinese medicine that can lengthen one’s life. PP can enhance immunity and anti-aging, and so on. In this experiment, we interfered APP transgenic mice with different concentration of PP, and the purpose is to explore the effects and functions of PP on APP transgenic mice, thus to find a new way to prevent and treat the experimental AD.Objective: To investigate the effect and function of PP on APP transgenic mice.Method: Inject different concentrations of PP solution into the mice’s stomach for 45 consecutive days. The Morris water maze was adopted to test the ability of the mice’s initiative learning ability and memory; Transmission Electron Microscope (TEM) was used to observe the ultrastructure of hippocampus; Stereology was adopted to analyze the ultrastructure index and SPSS13.0 was used to analyze the above-mentioned data.Result: The results show that PP has the following effects:1. Ethology: Compared with the blank group, the delitescence of the treated group shortened obviously, the frequency of finding the platform increased, and the frequency of making mistakes decreased (p<0.01). Within the treated group, the group with high concentration PP increased in the frequency of finding the platform, shortened in the delitescence, and decreased in the frequency of making mistakes (p<0.05).2. Hippocampus’ ultrastructure: Compared with the blank group: (1) The number of the neurons in the treated group increased while the degeneration degree of the neurons relieved; (2) Mice’s brain tissue edema and vacuoles degeneration decreased obviously in the treated group, there are more obvious effect in the high-dose PP group(p<0.01). The stereology parameters of mitochondria, synapse and synaptic interface structure have improved obviously in the treated group (p<0.05). There are significant differences among the groups with different concentration of PP (p<0.05).Conclusion: PP can improve APP transgenic mice’s central nervous system (CNS) ultrastructure, maintain CNS homeostasis, prevent peroxidation & inflammatory reaction, protect the central cholinergic system, and improve the learning ability and memory. There are dose-effect relationships. PP is an effective prescription for the prevention and therapy of experimental AD.更多还原