發(fā)布時(shí)間：2018-04-13 12:17

  本文選題：氯化鋁 + 斑馬魚��； 參考：《山西醫(yī)科大學(xué)》2017年碩士論文

【摘要】：目的:通過(guò)染鋁建立斑馬魚阿爾茨海默病模型,探討程序性壞死在鋁致斑馬魚阿爾茨海默病模型中的作用。方法:選取8月齡TU系成年斑馬魚,隨機(jī)分為4組,每組25條。在養(yǎng)殖液中加入不同濃度的結(jié)晶氯化鋁(PH6.4)染毒30天:對(duì)照組(0μg/L)、低濃度組(20μg/L)、中濃度組(100μg/L)、高濃度組(500μg/L)。染毒結(jié)束后,通過(guò)斑馬魚T迷宮檢測(cè)各組斑馬魚學(xué)習(xí)記憶能力;采用石墨爐原子吸收光譜法檢測(cè)各組斑馬魚腦鋁含量;采用酶聯(lián)免疫吸附法(ELISA)檢測(cè)各組斑馬魚腦組織中APP、Aβ1-42、Aβ1-40蛋白含量;采用RT-PCR法檢測(cè)各組斑馬魚腦組織中m TOR信號(hào)通路、阿爾茨海默病和程序性壞死相關(guān)基因的表達(dá)。結(jié)果:1.斑馬魚T迷宮結(jié)果:中濃度組和高濃度組斑馬魚在實(shí)驗(yàn)第2天、第3天、第4天的潛伏期與對(duì)照組相比明顯延長(zhǎng)(P0.05);高濃度組斑馬魚在實(shí)驗(yàn)的第2天、第3天、第4天在EC區(qū)停留的總時(shí)間與對(duì)照組相比減少(P0.05);中濃度組斑馬魚在實(shí)驗(yàn)的第3天、第4天在EC區(qū)停留的總時(shí)間與對(duì)照組相比減少(P0.05)。2.斑馬魚腦鋁含量檢測(cè)結(jié)果:中濃度組和高濃度組斑馬魚腦鋁含量與對(duì)照組和低濃度組相比顯著升高(P0.05);高濃度組斑馬魚腦鋁含量與中濃度組相比顯著升高(P0.05)。3.酶聯(lián)免疫吸附法(ELISA)檢測(cè)結(jié)果:中濃度組和高濃度組斑馬魚腦組織中APP蛋白含量與對(duì)照組相比顯著增加(P0.05);高濃度組斑馬魚腦組織中Aβ1-42蛋白含量與對(duì)照組相比顯著增加(P0.05);各組斑馬魚腦組織中Aβ1-40蛋白含量差別無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。4.RT-PCR檢測(cè)結(jié)果:中濃度組、高濃度組斑馬魚腦組織中m TOR、AKT2的基因表達(dá)與對(duì)照組、低濃度組相比顯著下降(P0.05);高濃度組斑馬魚腦組織中AKT1、PI3K的基因表達(dá)與對(duì)照組相比均顯著下降(P0.05)。中濃度組、高濃度組斑馬魚腦組織中appb、mapta的基因表達(dá)與對(duì)照組相比顯著增加(P0.05);高濃度組斑馬魚腦組織中appb的基因表達(dá)與中濃度組相比顯著增加(P0.05);中濃度組、高濃度組斑馬魚腦組織中BDNF的基因表達(dá)與對(duì)照組、低濃度組相比顯著下降(P0.05);中濃度組斑馬魚腦組織中BDNF的基因表達(dá)與對(duì)照組相比顯著下降(P0.05)。高濃度組斑馬魚腦組織中RIP1、PARP2、Bmf1、jph3、rab25和caspase8的基因表達(dá)與對(duì)照組相比均顯著增加(P0.05);中濃度組斑馬魚腦組織中PARP2、Bmf1和rab25的基因表達(dá)與對(duì)照組相比均顯著增加(P0.05);各組斑馬魚腦組織中FADD和mag的基因表達(dá)差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。結(jié)論:1.鋁致斑馬魚阿爾茨海默病模型建立成功;2.鋁可引起RIP1、PARP2、Bmf1、jph3、rab25和caspase8的基因表達(dá)增加;3.程序性壞死在鋁致斑馬魚阿爾茨海默病模型中發(fā)揮著重要的作用。
[Abstract]:Aim: to establish Alzheimer's disease model of zebrafish by aluminum exposure and to explore the role of programmed necrosis in aluminum-induced Alzheimer's disease model of zebrafish.Methods: 8 months old TU adult zebrafish were randomly divided into 4 groups, 25 in each group.After exposure to zebrafish, the learning and memory ability of zebrafish in each group was measured by T-maze, and the brain aluminum content of zebrafish in each group was detected by graphite furnace atomic absorption spectrometry (GFAAS).Enzyme linked immunosorbent assay (Elisa) was used to detect the protein content of APP A 尾 1-42 A 尾 1-40 in the brain tissues of zebrafish, and the expression of m TOR signaling pathway, Alzheimer's disease and programmed necrosis related genes in the brain tissues of zebrafish were detected by RT-PCR method.The result is 1: 1.Zebrafish T-maze results: the incubation period of zebrafish in the middle and high concentration groups was significantly longer than that in the control group on the 2nd, 3rd and 4th day, while in the high concentration group, the latency was significantly prolonged on the 2nd and 3rd day of the experiment.On the 4th day, the total stay time of zebrafish in EC region was lower than that in control group, and the total stay time of zebrafish in the middle concentration group was lower than that in the control group on the 3rd day and the 4th day, compared with the control group.The results showed that the brain aluminum content of zebrafish in the middle and high concentration groups was significantly higher than that in the control group and the low concentration group, and that in the high concentration group was significantly higher than that in the middle concentration group and that in the middle concentration group, and that in the high concentration group was significantly higher than that in the middle concentration group.Enzyme linked immunosorbent assay (Elisa): the content of APP protein in the brain tissue of zebrafish in middle and high concentration groups was significantly higher than that in control group, and the content of A 尾 1-42 protein in brain tissue of zebrafish in high concentration group was significantly higher than that in control group.There was no significant difference in A 尾 1-40 protein content in the brain tissue of zebrafish in each group. 4. Results of RT-PCR: middle concentration group;Compared with the control group, the expression of mTORA AKT2 gene in the brain tissue of the high concentration group was significantly lower than that of the control group, and that of the high concentration group was significantly lower than that of the control group, while the gene expression of PI3K in the brain tissue of the high concentration group was significantly lower than that of the control group.In the middle and high concentration groups, the expression of appb gene in the brain tissue of zebrafish was significantly higher than that of the control group, while the expression of appb gene in the brain tissue of the high concentration group was significantly higher than that of the middle concentration group, while that of the middle concentration group was significantly higher than that of the middle concentration group, while that of the middle concentration group was significantly higher than that of the control group.The expression of BDNF gene in the brain tissue of zebrafish in high concentration group was significantly lower than that in control group, and the expression of BDNF gene in brain tissue of zebrafish in middle concentration group was significantly lower than that in control group.There was no significant difference in gene expression between FADD and mag.Conclusion 1.The model of Alzheimer's disease in zebrafish induced by aluminum was established successfully.Aluminum can increase the gene expression of RIP1, PARP2, Bmf1, jph3, rab25 and caspase8.Programmed necrosis plays an important role in aluminum-induced Alzheimer's disease model of zebrafish.
【學(xué)位授予單位】：山西醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R749.16;R-332

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