【作者】 周妍妍；

【导师】 谢宁；

【作者基本信息】 黑龙江中医药大学 ， 中医基础理论， 2007， 博士

【摘要】 老年性痴呆(Alzheimer’s disease，AD)是一种中枢神经系统原发性退行性变性疾病，临床主要表现为进行性记忆、理解、判断、定向等认知功能障碍，精神行为异常以及生活能力减退。该病不仅是一种随年龄增长而发病率升高的疾病，而且是一种致残率、致死率很高的疾病，给家庭和社会带来巨大的精神和经济负担，因而深入探讨AD的发病机制，研究有效的治疗措施是世界瞩目的重大课题。本课题在以往地黄饮子防治AD系列研究的基础上，采用脑脊液药理学方法，通过建立β淀粉样蛋白诱导PC12细胞损伤的AD细胞模型，运用实时荧光定量PCR、Werstern blot、免疫细胞化学、生物化学及光、电镜技术等先进的检测方法和手段，从细胞及分子水平对地黄饮子防治AD的作用及其机制进行探讨。结果显示：一、地黄饮子可显著改善Aβ25-35损伤引起的PC12细胞形态的改变，减轻细胞膜损伤，增强细胞活力，减少损伤所致的细胞死亡。二、地黄饮子能提高PC12细胞培养液中SOD的活性，上调SODmRNA的表达，降低培养液中MDA的含量，提高自由基清除能力，减少自由基对PC12细胞的损伤。三、地黄饮子能明显提高Aβ25-35损伤时PC12细胞ChAT的表达，通过减轻胆碱能系统的损害防治AD。四、地黄饮子能抑制Aβ25-35损伤时PC12细胞微管相关蛋白tau的表达，从而起到防治AD的作用。更多还原

【Abstract】 The senile dementia, also known as Alzheimer’s disease(AD) is a kind of primary regressive diseases of nervous system among the elder. The manifested symptoms include recognizable dysfunction , the spiritual and behavioral abnormality and the loss of vital force. The recognizable dysfunction appears on the aspects of progressive memory, understanding, judgement and orientation. With its popularity, this kind of disease has thrown heavy burden on the society and the families. To explore the pathogenesis and find out an effective treatment has become more and more important.The current research was conducted on the basis of the previous systematic researches on the effect of DHYZ on AD. The model cells with AD was successfully established through inducing the injury of PC12 by amyloid beta-protein with the relevant pharmacological method. The methods of real-time quantification PCR, Western blot, immune histochemistry and optical and electronic microscopes was applied in the research.The results of the current research is shown as the follows: 1. The model cells with AD was successfully established through inducing the injury of PC12 by Aβ25-35 in the research, which could be used as an ideal cell model of AD. 2. DHYZ could obviously improve the pathogenic cellular morphological change of PC12 induced by Aβ25-35, reduce the damage of cellular membrane, strengthen the vitality of the cells and prevent the cell from death. 3. DHYZ could enhance the activity of SOD in the cell culture fluid of PC12, increase the expression of SOD mRNA, decrease the content of MDA in the culture fluid, improve the clearing capability to the free radicals. 4. DHYZ could obviously improve the expression of ChAT of PC12 induced by Aβ25-35.It is through alleviating the damage on the cholinergic system that DHYZ play the roles of treating AD.5. It is through significantly deceasing the expression of canaliculus-associated protein- tau of PC12 induced by Aβ25-35 that DHYZ functions to prevent and treat AD.更多还原