NAMPT在阿尔兹海默疾病模型大鼠脑中的表达变化

发布时间：2018-05-19 09:09

本文选题：AD模型鼠 + 大脑　；参考：《安徽师范大学》2013年硕士论文

【摘要】：阿尔兹海默病(Alzheimer’s disease，AD)也称老年痴呆，其主要病理特征为细胞外β淀粉样蛋白(amyloid protein β,Aβ)沉积形成老年斑、细胞内Tau蛋白过度磷酸化形成神经原纤维缠结(neurofibrillary tangles,NFT)。AD是年龄高度相关性疾病，是中枢神经系统的一种渐进性退行性疾病。目前，对于AD的病因有好几种说法，但还没有统一意见。烟酰胺磷酸核糖转移酶(Nampt)是存在于脊椎动物体内一种具有多种生物活性的功能蛋白。Nampt在很大程度上决定着烟酰胺腺嘌呤二核苷酸(Nicotinamide Adenine Dinucleotide, NAD)的水平，并影响众多的生理生化过程，而这有赖于NAMPT基因的表达水平。研究证明NAMPT为哺乳动物NAD合成补救途径中的限速酶。本实验通过建立AD模型检测Nampt在AD大脑中的分布变化。将大鼠分为实验组(AD组)和对照组(NC组)，用D-半乳糖和AlCl3建模两个月。体重、摄食量、open field和水迷宫均证实两组行为学有极其显著的差异(P0.01)，银染、tau蛋白和Aβ抗体免疫组化证实两组在组织学上有极其显著的差异(P0.01)。实验模型较好地模拟出了AD的行为学和病理学特征。 Nampt免疫阳性反应主要分布在大鼠的皮层和海马。在皮层，Nampt免疫着色主要分布于第一躯体感觉皮层，阳性细胞呈圆形或梨形，AD组细胞大多呈不规则形，体积缩小，阳性物质主要定位于细胞核；而NC组中，细胞形态、体积多正常，阳性物质较少且均匀分布于胞质。在海马，Nampt免疫反应主要分布于海马的分子层和椎体层。在分子层，AD组细胞大多呈不规则形，体积缩小，四周有空洞，阳性物质主要定位于细胞核，且分布不均；而在NC组中，细胞形态、体积多正常，呈圆形或椭圆形，阳性物质均匀分布于胞质。在椎体层，AD组细胞排列混乱且松散，胞核多消失，形成空洞，阳性物质几乎无表达；NC组细胞排列整齐且紧密，核与核仁完好，形态正常，阳性物质主要定位于胞质。统计显示，与NC组相比，AD组大鼠海马CA1区、CA2区和CA3区椎体层细胞数都明显减少(P0.01)。 Nampt基因在AD模型鼠脑中表达的如此变化，提示Nampt和AD有着极为密切的关系，Nampt可能通过控制细胞和机体的NAD水平，影响Sirtuins活性，从而影响细胞中ROS的产生以及抗氧化酶的表达，进而影响衰老进程或促进AD形成。
[Abstract]:Alzheimer's disease (AD), also known as Alzheimer's disease, is characterized by the deposition of amyloid protein 尾 A 尾, an extracellular amyloid protein. The formation of neurofibrillary tangles, neurofibrillary tanglesus, NFT, AD is an age-related disease and a progressive degenerative disease of the central nervous system (CNS). At present, there are several theories about the etiology of AD, but there is no consensus. Nicotinamide ribonucleosyltransferase (Nampt2) is a functional protein. Nampt, which has many biological activities in vertebrates, determines to a large extent the level of nicotinamide dinucleotide Nicotinamide Adenine Dinucleotide, NAD), and affects many physiological and biochemical processes. This depends on the level of NAMPT gene expression. NAMPT is proved to be a rate-limiting enzyme in mammalian NAD biosynthesis rescue pathway. In this study, AD model was established to detect the distribution of Nampt in AD brain. Rats were divided into experimental group (AD group) and control group (NC group). Dgalactose and AlCl3 were used to model the rats for two months. Body weight, food intake, open field and water maze all proved that there were significant differences in behavior between the two groups (P0.01a), and there was a significant difference in histology between the two groups by immunohistochemical staining of tau protein and A 尾 antibody. The behavioral and pathological characteristics of AD were well simulated by the experimental model. Nampt immunoreactivity was mainly distributed in cortex and hippocampus of rats. In the first somatosensory cortex, the positive cells were mostly irregular in shape and reduced in size, and the positive substances were mainly located in the nucleus, while in the NC group, the cells were morphologically. More normal volume, less positive substances and distributed evenly in the cytoplasm. In the hippocampus, the Nampt immunoreaction was mainly distributed in the molecular and vertebral layers of the hippocampus. In the AD group, the cells were mostly irregular in shape, small in volume, with holes around them. The positive substances were mainly located in the nucleus and distributed unevenly, while in the NC group, the cells were normal in shape, round or oval in shape, and oval in shape. The positive substances were uniformly distributed in the cytoplasm. In AD group, the cells were disorganized and loosely arranged, the nuclei disappeared, and formed cavities. In the NC group, the positive substances were arranged neatly and closely, the nuclei and nucleoli were intact, the morphology was normal, and the positive substances were mainly located in the cytoplasm. Compared with NC group, the number of laminar cells in hippocampal CA1, CA2 and CA3 decreased significantly in AD group. The expression of Nampt gene in the brain of AD model showed that Nampt and AD were closely related to Sirtuins activity by controlling the level of NAD in cells and body, thus affecting the production of ROS and the expression of antioxidant enzymes in the cells. And then affect the aging process or promote the formation of AD.
【学位授予单位】：安徽师范大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R749.16;R-332

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