本文選題：阿爾茨海默病 + 卡路里限制��； 參考：《暨南大學》2017年碩士論文

【摘要】：目的:阿爾茨海默病(Alzheimer’s disease,AD)俗稱老年癡呆癥,是最為常見的一種神經(jīng)退行性疾病。隨著人口老齡化的到來,AD發(fā)病率呈急劇上升的趨勢�？防锵拗茖儆陲嬍诚拗频囊环N,但它不會引起營養(yǎng)失調,在AD的眾多干預措施中,卡路里限制正越來越顯示出其在改善或減輕神經(jīng)退行性變化方面的強大作用。本文旨在探究卡路里限制對AD轉基因小鼠腦蛋白組的影響,進一步為AD的防治提供科學依據(jù)。方法:本文選用3月齡的三轉基因AD(3xTg-AD)小鼠和野生型(WT)小鼠作為實驗小鼠,以40%的卡路里限制(calorie restriction,CR)飲食處理其3個月,同時以隨意采食(ad libitum,AL)的3x Tg-AD小鼠和WT小鼠作為對照。首先,通過曠場實驗、黑白箱實驗和高架十字迷宮實驗探究卡路里限制對3xTg-AD小鼠焦慮行為的影響;通過強迫游泳實驗和懸尾實驗探究卡路里限制對3xTg-AD小鼠抑郁行為的影響;通過水迷宮實驗探究卡路里限制對3xTg-AD小鼠記憶行為的影響。隨后,利用熒光差異凝膠電泳(2D-DIGE)結合基質輔助激光解析電離飛行時間質譜(MADLD-TOF-MS)技術研究卡路里限制對小鼠海馬組織蛋白質組的影響。最后,利用Western blot對差異蛋白進行驗證。結果:行為學結果表明,卡路里限制改善了3x Tg-AD小鼠的焦慮、抑郁和空間記憶損傷。蛋白質組學結果表明,在卡路里限制處理的WT小鼠和隨意采食的WT小鼠中有11個差異蛋白的表達;在隨意采食的3xTg-AD小鼠和隨意采食的WT小鼠中有30個差異蛋白的表達;在卡路里限制處理的3x Tg-AD小鼠和隨意采食的3x Tg-AD小鼠中有13個差異蛋白的表達。生物信息學分析顯示,差異蛋白主要參與代謝、細胞凋亡、細胞間信號傳導等進程,且有多個表達異常的蛋白已有研究報道與AD的發(fā)生發(fā)展密切相關,其中突觸相關蛋白synapsin-2(SYN2)和伴侶分子14-3-3 protein epsilon(14-3-3E)經(jīng)Western blot驗證與2D-DIGE結果一致。結論:綜上結果表明,卡路里限制改善了3x Tg-AD小鼠的焦慮、抑郁和空間記憶損傷,其中SYN2和14-3-3E等分子的表達改變可能在卡路里限制改善AD轉基因小鼠行為學異常中發(fā)揮重要作用。
[Abstract]:Objective: Alzheimer's disease (AD), commonly known as Alzheimer's disease, is the most common neurodegenerative disease.With the coming of population aging, the incidence of AD increased sharply.Calorie restriction is one of the dietary restrictions, but it does not cause nutritional disorders. Among the many AD interventions, calorie restriction is increasingly showing its powerful role in improving or mitigating neurodegenerative changes.The purpose of this study was to explore the effect of calorie restriction on brain proteome of AD transgenic mice and to provide scientific basis for AD prevention and treatment.Methods: the 3-month-old and wild-type mice were treated with calorie restriction CR-40% calorie restriction diet for 3 months, and the 3x Tg-AD mice and WT mice fed at random were used as control.Firstly, the effects of calorie restriction on anxiety behavior in 3xTg-AD mice were investigated by open field experiment, black-and-white box experiment and elevated cross maze test, and the effects of calorie restriction on depression behavior in 3xTg-AD mice were investigated by forced swimming test and tail suspension experiment.The effect of calorie restriction on memory behavior of 3xTg-AD mice was investigated by water maze experiment.Then the effects of calorie restriction on proteome in hippocampus of mice were studied by means of fluorescence differential gel electrophoresis (FDGE) 2D-DIGE and MADLD-TOF-MSM (Matrix-assisted laser desorption ionization time of flight mass spectrometry).Finally, the differential protein was verified by Western blot.Results: behavioral results showed that calorie restriction improved anxiety, depression and spatial memory impairment in 3x Tg-AD mice.The proteomics results showed that there were 11 differentially expressed proteins in WT mice treated with calorie restriction and WT mice fed at random, and 30 differentially expressed proteins in 3xTg-AD mice and WT mice fed at will.There were 13 differentially expressed proteins in 3x Tg-AD mice treated with calorie restriction and 3x Tg-AD mice fed at random.Bioinformatics analysis shows that differential proteins are mainly involved in the processes of metabolism, apoptosis and intercellular signal transduction, and many proteins with abnormal expression have been reported to be closely related to the occurrence and development of AD.The synapsin-2 SYN2) and the chaperone 14-3-3 protein epsilon 14-3-3E) were confirmed by Western blot to be consistent with the results of 2D-DIGE.Conclusion: calorie restriction improves anxiety, depression and spatial memory impairment in 3x Tg-AD mice.The changes of expression of SYN2 and 14-3-3E may play an important role in calorie restriction to improve behavioral abnormalities in AD transgenic mice.
【學位授予單位】：暨南大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R749.16

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本文編號：1767745