虾青素对AD小鼠模型中A-beta毒性的抑制作用及其机制

发布时间：2018-05-08 16:16

本文选题：虾青素 + A-beta　；参考：《哈尔滨工业大学》2017年硕士论文

【摘要】：阿尔兹海默症(Alzheimer’s disease,AD)是老年人中发病率极高的神经退行性疾病。AD致病机制目前还未有定论,但Aβ级联假说是目前广受认可的,其认为β-淀粉样蛋白(β-amyloid,Aβ)是诱导阿尔兹海默症的重要原因。为了了解虾青素对Aβ毒性的抑制作用机制,本研究对AD转基因小鼠APPswe/PS1d E9(APP/PS1)喂食虾青素3个月后对小鼠脑组织进行分析。刚果红染色结果显示,虾青素可以显著减少Aβ沉积的总面积。通过Western blot方法检测小鼠大脑皮质中淀粉样前体蛋白(amyloid precursor protein,APP),Aβ单体,Aβ寡聚体和BACE1的含量,发现虾青素在不影响APP水平及Aβ的β/α-分泌酶生成途径的同时,能够显著抑制Aβ寡聚体的形成,从而减少其毒性。通过TUNEL染色观察小鼠脑组织中的细胞凋亡状况发现,虾青素可以显著降低小鼠脑中的凋亡水平;并且通过Western blot方法检测凋亡通路和生存通路,结果显示虾青素可以显著降低caspase-3水平、Bax/Bcl-2比率从而抑制神经细胞的凋亡。虾青素亦可显著提升Akt/Bad信号通路,从而促进神经细胞的生存。通过改良Bielschowy镀银染色,检测小鼠脑中的神经纤维缠结(neurofibrillary tangles,NFTs),发现虾青素可以减少小鼠脑组织中NFTs的产生,从而减少NFTs对小鼠神经细胞的毒性。Western blot方法检测结果表明虾青素可能通过显著降低p38丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)磷酸化水平减少磷酸化-tau蛋白(phospho-tau,p-tau)水平,从而减少NFTs。利用MDA试剂盒检测小鼠大脑皮质中活性氧(reactive oxygen species,ROS)引起的脂质过氧化物丙二醛(methane dicarboxylic aldehyde,MDA),结果表明虾青素可以减少小鼠脑中的MDA水平。综上所述,虾青素可能通过降低Aβ寡聚体诱导的氧化应激(oxidative stress,OS),神经细胞凋亡和tau蛋白的过度磷酸化从而减轻Aβ毒性。
[Abstract]:Alzheimer 's disease (AD) is an undetermined mechanism for the pathogenesis of.AD in the elderly with a very high incidence of neurodegenerative disease, but the A beta cascade hypothesis is currently widely accepted. It is considered that beta amyloid (beta -amyloid, A beta) is an important cause of the induction of Arz's disease. In order to understand the toxicity of astaxanthin to A beta toxicity. In this study, the brain tissue of AD transgenic mice APPswe/PS1d E9 (APP/PS1) was fed to astaxanthin (APP/PS1) for 3 months. The results of Congo red staining showed that astaxanthin could significantly reduce the total area of A beta deposition. The Western blot method was used to detect the amyloid precursor protein (amyloid precursor P) in the large cortex of mice (amyloid precursor P). Rotein, APP), the content of A beta monomer, A beta oligomer and BACE1, it was found that astaxanthin could significantly inhibit the formation of A beta oligomer and reduce the toxicity of A beta oligomer without affecting the APP level and the beta alpha secretase production pathway, and it was found that astaxanthin could significantly reduce the mouse brain apoptosis through the TUNEL staining. The apoptosis level in the brain and the detection of apoptosis pathway and survival pathway through the Western blot method showed that astaxanthin could significantly reduce the caspase-3 level and the Bax/Bcl-2 ratio to inhibit the apoptosis of neural cells. Astaxanthin can also significantly enhance the Akt/Bad signaling pathway to promote the survival of the nerve cells. By improving Bielschowy silver plating Staining, detection of neurofibrillary tangles (NFTs) in the brain of mice, it is found that astaxanthin can reduce the production of NFTs in the brain tissue of mice, thus reducing the toxicity of NFTs to the mouse neural cells by.Western blot method, which indicates that astaxanthin may significantly reduce the p38 mitogen activated protein kinase (mitogen-activate). D protein kinase, MAPK) decreased the level of phosphorylated -tau protein (phospho-tau, p-tau), thus reducing NFTs. using MDA kit to detect active oxygen (reactive oxygen species) in the cerebral cortex of mice. The results showed that astaxanthin could reduce the mice. MDA levels in the brain. To sum up, astaxanthin may reduce the toxicity of A beta by reducing the oxidative stress (oxidative stress, OS) induced by A beta oligomers, apoptosis of nerve cells and the excessive phosphorylation of tau protein.

【学位授予单位】：哈尔滨工业大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R749.16

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