本文選題：阿爾茨海默病 + 高爾基體破碎　； 參考：《華中科技大學(xué)》2013年碩士論文

【摘要】：背景：阿爾茨海默病（Alzheimer’s Disease,AD）是一種進(jìn)行性的神經(jīng)退行性疾病，其特征性的病理改變是細(xì)胞內(nèi)的神經(jīng)原纖維纏結(jié)（NFTs），其主要成分是微管相關(guān)蛋白tau的過(guò)度磷酸化。鑒于tau蛋白過(guò)度磷酸化是AD神經(jīng)元發(fā)生退行性變性的重要標(biāo)志，研究tau蛋白過(guò)度磷酸化的上游因素對(duì)闡明AD神經(jīng)元損傷機(jī)制、尋找有效防治靶點(diǎn)具有重要意義。 方法：4,8,13和16月齡的C57BL/6雄性小鼠和6個(gè)月APP/PS1轉(zhuǎn)基因小鼠（每個(gè)年齡組4-5只）進(jìn)行神經(jīng)元的超微結(jié)構(gòu)研究。通過(guò)Western Blot方法檢測(cè)4,8,13和16月齡的C57BL/6雄性小鼠（每個(gè)年齡組4-5只）的高爾基基質(zhì)蛋白和tau蛋白在腦中的表達(dá)。所有的C57BL/6小鼠由華中科技大學(xué)同濟(jì)醫(yī)學(xué)院動(dòng)物實(shí)驗(yàn)中心提供。動(dòng)物于寬松適宜的環(huán)境中飼養(yǎng)，自由飲水，室溫保持在恒定的溫(26±2°C)。本實(shí)驗(yàn)過(guò)程中，所有的動(dòng)物實(shí)驗(yàn)均嚴(yán)格遵守神經(jīng)科學(xué)協(xié)會(huì)頒布的《動(dòng)物使用政策》。AD模型鼠APP/PS1轉(zhuǎn)基因敲除小鼠腦組織樣本來(lái)自于北京大學(xué)張巖教授贈(zèng)予。運(yùn)用細(xì)胞免疫熒光研究高爾基破碎時(shí)高爾基基質(zhì)蛋白與tau的過(guò)度磷酸化間的關(guān)系。 結(jié)果：C57BL/6小鼠大腦神經(jīng)元內(nèi)高爾基體破碎和tau蛋白磷酸化水平隨年齡增長(zhǎng)不斷增加。布雷菲德菌素A和諾考達(dá)唑通過(guò)HEK293/tau細(xì)胞內(nèi)的高爾基體破碎介導(dǎo)tau蛋白過(guò)度磷酸化。 結(jié)論：在AD小鼠中，，神經(jīng)元內(nèi)高爾基體破碎隨年齡增加不斷增多，且高爾基體破碎是tau蛋白過(guò)度磷酸化的上游因素之一。
[Abstract]:Background: Alzheimer's disease (Alzheimer's disease) is a progressive neurodegenerative disease. Its characteristic pathological change is intracellular neurofibrillary tangles (NFTs), the main component of which is the hyperphosphorylation of microtubule-associated protein (tau). Since excessive phosphorylation of tau protein is an important marker for the degeneration of AD neurons, it is important to study the upstream factors of tau hyperphosphorylation in order to elucidate the mechanism of AD neuron injury and to find effective targets for prevention and treatment. Methods the ultrastructure of neurons in C57BL/6 male mice aged 13 and 16 months and APP/PS1 transgenic mice at 6 months old (4-5 mice per age group) were studied. The expression of Golgi matrix protein and tau protein in the brain of C57BL/6 male mice aged 13 and 16 months (4-5 mice in each age group) was detected by Western Blot method. All C57BL/6 mice were provided by the Animal Laboratory Center of Tongji Medical College, Huazhong University of Science and Technology. The animals were kept in a relaxed and suitable environment, drinking water freely and keeping a constant temperature of 26 鹵2 擄C ~ (-1) at room temperature. In the course of this experiment, all animal experiments strictly comply with the animal use policy promulgated by the Neuroscience Association. The brain tissue samples of APP/PS1 transgenic knockout mice of AD model mice were donated by Professor Zhang Yan of Peking University. The relationship between Golgi matrix protein and excessive phosphorylation of tau was studied by cell immunofluorescence. Results the levels of Golgi body fragmentation and tau protein phosphorylation in brain neurons of C57BL / 6 mice increased with age. Blefedzein A and nocodazole mediated excessive phosphorylation of tau protein through Golgi body fragmentation in HEK293/tau cells. Conclusion: in AD mice, the fragmentation of Golgi body in neurons increases with age, and Golgi body fragmentation is one of the upstream factors of excessive phosphorylation of tau protein.
【學(xué)位授予單位】：華中科技大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2013
【分類號(hào)】：R749.16

【參考文獻(xiàn)】

相關(guān)期刊論文 前2條

1 鮑時(shí)來(lái);;高爾基體的結(jié)構(gòu)與功能研究簡(jiǎn)介[J];生物學(xué)通報(bào);2006年09期

2 齊新;崔麗英;;SOD1基因與運(yùn)動(dòng)神經(jīng)元病相關(guān)性的研究進(jìn)展[J];中國(guó)實(shí)用內(nèi)科雜志;2009年05期

本文編號(hào)：1930676