本文選題：NR4A1 + APP��； 參考：《重慶醫(yī)科大學(xué)》2017年碩士論文

【摘要】：研究目的:探討孤兒核受體NR4A1過(guò)表達(dá)對(duì)APP代謝和Tau磷酸化的影響,并闡述其可能機(jī)制。研究方法:18月齡APP/PS1和WT小鼠麻醉后處死取海馬組織。應(yīng)用蛋白質(zhì)印跡法檢測(cè)NR4A1蛋白質(zhì)的表達(dá),實(shí)時(shí)定量聚合酶鏈反應(yīng)(q RT-PCR)檢測(cè)NR4A1 mRNA表達(dá),免疫組化染色觀察NR4A1在小鼠大腦海馬中的表達(dá)。用鼠pCMV-NR4A1質(zhì)粒轉(zhuǎn)染HT22細(xì)胞,應(yīng)用蛋白質(zhì)印跡法檢測(cè)NR4A1、APP、ADAM10、BACE1、t-Tau和p-Tau、GSK3β和p-GSK3β、CDK5、ERK的表達(dá),q RT-PCR檢測(cè)NR4A1 mRNA、ADAM10 mRNA、BACE1 mRNA表達(dá)。研究結(jié)果:APP/PS1小鼠海馬組織中APP、NR4A1表達(dá)增多,q RT-PCR顯示NR4A1 mRNA水平也升高。用鼠pCMV-NR4A1質(zhì)粒轉(zhuǎn)染HT22細(xì)胞后,NR4A1蛋白質(zhì)及mRNA水平均顯著升高。NR4A1過(guò)表達(dá)后,APP、BACE1表達(dá)升高,ADAM10表達(dá)下降;q RT-PCR顯示NR4A1過(guò)表達(dá)后ADAM10 mRNA水平下降,BACE1 mRNA水平升高。NR4A1過(guò)表達(dá)后p-Tau(S396)蛋白表達(dá)升高,但是總的Tau及p-Tau(S262和T231)卻沒(méi)有改變;p-GSK3β(S9)表達(dá)下降,CDK5、ERK表達(dá)無(wú)明顯改變。研究結(jié)論:綜上可知,NR4A1過(guò)表達(dá)使ADAM10下調(diào)、BACE1上調(diào),從而促進(jìn)APP向Aβ途徑降解;此外,NR4A1可能通過(guò)p-GSK3β影響Aβ和p-Tau的生成。
[Abstract]:Aim: to investigate the effects of NR4A1 overexpression on APP metabolism and Tau phosphorylation in orphan nuclei and to elucidate its possible mechanism. Methods the hippocampal tissues of APP/PS1 and WT mice were killed after anesthesia at 18 months old. The expression of NR4A1 protein was detected by Western blot, the expression of NR4A1 mRNA was detected by real-time quantitative polymerase chain reaction (PCR), and the expression of NR4A1 in the hippocampus of mice was observed by immunohistochemical staining. HT22 cells were transfected with mouse pCMV-NR4A1 plasmid. The expression of NR4A1 mRNA-ADAM10 mRNA-BACE1 mRNA was detected by Western blotting. The expression of NR4A1 mRNA-ADAM10 mRNA-BACE1 mRNA and p-Tautaug GSK3 尾 and p-GSK3 尾 CDK5 ERK were detected by Western blot. Results the increased expression of APPtNR4A1 in hippocampal tissue of mice with 1: App / PS1 showed that the level of NR4A1 mRNA was also increased by Q RT-PCR. After transfection of mouse pCMV-NR4A1 plasmid into HT22 cells, the levels of NR4A1 protein and mRNA were significantly increased. After overexpression of NR4A1, the expression of APPfBACE1 increased and the expression of ADAM10 decreased. Q RT-PCR showed that the level of ADAM10 mRNA decreased after NR4A1 overexpression, and the expression of p-TauS396) protein increased after overexpression of NR4A1, and the expression of p-TauS396 protein increased after overexpression of NR4A1. However, total Tau, p-Tau(S262 and T231) did not change the expression of p-GSK3 尾 -S9). Conclusion: the overexpression of NR4A1 leads to down-regulation of ADAM10 and up-regulation of APP to A 尾 pathway, and NR4A1 may affect the formation of A 尾 and p-Tau through p-GSK3 尾.
【學(xué)位授予單位】：重慶醫(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

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