胆固醇对早老性痴呆转基因动物模型APP加工及Aβ生成的影响

发布时间：2018-03-11 08:22

本文选题：胆固醇　切入点：早老性痴呆转基因动物模型　出处：《中国协和医科大学》2006年硕士论文　论文类型：学位论文

【摘要】：阿尔茨海默病(Alzheimer's disease，，AD)是一种常见的中枢神经系统退行性变性疾病，其主要临床表现为进行性记忆减退和认知障碍。AD的神经病理表现主要是海马区和新皮质区弥散性的神经元丢失、神经纤维缠结和细胞外的类淀粉样沉积。Aβ是一组由β淀粉样前体蛋白(β-amyloidprecursor protein，APP)降解产生的含39-43个氨基酸残基的混合物。类淀粉样蛋白假说认为Aβ的生成过多和细胞外Aβ沉积是AD发病最原始、最重要的病因。目前很多流行病学资料显示高血脂可能和AD的发病机制相关。高脂高胆固醇饮食已成为一个公认的AD危险因子，而且众多流行病学调查以及体内、体外实验均证明胆固醇水平对于APP代谢，Aβ产生具有重要调节意义。有人认为他汀类药物作为一种目前应用最广的降脂药可以通过减少细胞的胆固醇水平减少Aβ的生成，但也有人认为他汀类药物对AD的保护作用与其降低胆固醇的作用并不直接相关。为了在体研究胆固醇对APP代谢及Aβ的生成中的作用以及他汀类药物是否具有AD保护作用，本实验建立了不同血胆固醇浓度梯度的APP转基因小鼠模型。36只APP转基因阳性鼠被平均分为4组：①高脂饲料给药组②正常饲料给药组③高脂饲料安慰剂组④正常饲料安慰剂组；另有9只同窝阴性鼠设为⑤阴性对照组。分别给予高脂高胆固醇饲料或正常饲料喂养6个月后给予辛伐他汀或安慰剂灌胃28天，使各组动物出现不同血胆固醇梯度。Western Blot检测APP、C99、BACE、PS-1和Aβ42表
[Abstract]:Alzheimer's disease (AD) is a common degenerative disease of the central nervous system. Its main clinical manifestations are progressive memory loss and cognitive impairment. The neuropathological manifestations of AD are mainly diffuse neuronal loss in hippocampus and neocortex. Neurofibrillary tangles and extracellular amyloid deposition .A 尾 are a mixture of 39-43 amino acid residues produced by the degradation of 尾 -amyloid precursor protein. The amyloid hypothesis suggests that A 尾 is excessive and extracellular. The A 尾 deposition was the most primitive in AD. The most important etiology. At present, many epidemiological data indicate that hyperlipidemia may be associated with the pathogenesis of AD. High-fat and high-cholesterol diet has become a recognized risk factor for AD. In vitro experiments have proved that cholesterol level plays an important role in regulating the production of A 尾 in APP metabolism. Some people believe that statins, as one of the most widely used lipid-lowering drugs, can reduce the production of A 尾 by reducing cholesterol level in cells. But others believe that the protective effect of statins on AD is not directly related to its cholesterol-lowering effect. In order to study the effect of cholesterol on APP metabolism and A 尾 production in vivo, and whether statins have AD protective effect, In this experiment, the APP transgenic mice model with different blood cholesterol concentration gradient was established. 36 APP transgenic mice were divided into 4 groups on average: group 1, high fat diet group, group 2, normal diet group, group 3, high fat diet placebo group, group 4, normal diet placebo group; In addition, 9 cohort negative mice were given high-fat and high-cholesterol diet or normal diet for 6 months, and then simvastatin or placebo were given orally for 28 days. Serum cholesterol gradients. Western Blot was used to detect the PS-1 and A 尾 42 tables of APP C99 BACEP.
【学位授予单位】：中国协和医科大学
【学位级别】：硕士
【学位授予年份】：2006
【分类号】：R-332

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