本文選題：姜黃素 + 阿爾茨海默病　； 參考：《重慶醫(yī)科大學(xué)》2013年碩士論文

【摘要】：目的：脂代謝紊亂尤其是膽固醇代謝紊亂不僅是冠心病的致病因素，同樣也是阿爾茨海默�。ˋD）的重要危險(xiǎn)因素。大量研究已經(jīng)證實(shí)，腦膽固醇代謝異常促進(jìn)了AD的進(jìn)展。姜黃素具有降低血脂的作用，但其機(jī)制仍不明確。本文主要探討姜黃素通過影響三磷酸腺苷結(jié)合盒轉(zhuǎn)運(yùn)子A1（ABCA1）跨膜轉(zhuǎn)運(yùn)體系改善AD轉(zhuǎn)基因小鼠脂代謝紊亂的機(jī)制。 方法：APP/PS1雙轉(zhuǎn)基因小鼠Tg2576模型分三組，即癡呆組、低劑量組和高劑量組，不同濃度姜黃素飼料喂養(yǎng)6個(gè)月；Morris水迷宮檢測(cè)各組小鼠空間認(rèn)知和記憶能力的變化；膽固醇酶法比色法檢測(cè)各組血清中總膽固醇（TC）和高密度脂蛋白（HDL）的含量；免疫組化檢測(cè)各組轉(zhuǎn)基因鼠腦組織Aβ42的表達(dá)情況以及海馬CA1區(qū)錐體細(xì)胞的LXR-β、RXR-α、ABCA1和apoA1的表達(dá)情況； Realtime PCR和Western Blotting檢測(cè)各組轉(zhuǎn)基因小鼠腦組織LXR-β、RXR-α、ABCA1的mRNA和蛋白水平的變化。 結(jié)果：Morris水迷宮實(shí)驗(yàn)結(jié)果表明AD轉(zhuǎn)基因小鼠的空間認(rèn)知和記憶能力經(jīng)姜黃素喂養(yǎng)后明顯改善。AD轉(zhuǎn)基因小鼠經(jīng)過姜黃素飼喂后血清中TC含量明顯下降，而HDL的含量增高，其差異具有統(tǒng)計(jì)學(xué)意義（P㩳0.05）。免疫組織化學(xué)染色顯示低劑量組和高劑量組小鼠的腦組織中Aβ42的生成明顯減少，轉(zhuǎn)基因小鼠腦組織海馬CA1區(qū)的LXR-β、RXR-α、ABCA1和apoA1的表達(dá)在姜黃素飼喂組中明顯高于未飼喂姜黃素組，且高劑量組的蛋白表達(dá)顯著高于低劑量組的表達(dá)，其差異有統(tǒng)計(jì)學(xué)意義（P㩳0.05）。經(jīng)過姜黃素飼喂的轉(zhuǎn)基因小鼠的腦組織中LXR-β、RXR-α和ABCA1的mRNA表達(dá)增加而且相應(yīng)的蛋白表達(dá)量也隨之增加，其差異有統(tǒng)計(jì)學(xué)意義（P㩳0.05）。 結(jié)論：ABCA1跨膜轉(zhuǎn)運(yùn)膽固醇體系在阿爾茨海默病的發(fā)生發(fā)展過程中有著重要的作用，姜黃素改善AD脂代謝紊亂可能與通過LXR-β和RXR-α增強(qiáng)ABCA1跨膜轉(zhuǎn)運(yùn)有關(guān)。
[Abstract]:Objective: lipid metabolism disorder, especially cholesterol metabolism disorder, is not only a pathogenic factor of coronary heart disease, but also an important risk factor of Alzheimer's disease (AD). A large number of studies have confirmed that abnormal brain cholesterol metabolism contributes to the progression of AD. Curcumin has the effect of lowering blood lipid, but its mechanism is still unclear. The mechanism of curcumin improving lipid metabolism disorder in AD transgenic mice by affecting the transmembrane transport system of adenosine triphosphate binding cassette transporter A1A1ABCA1 was studied. Methods the Tg2576 model of two transgenic mice was divided into three groups: dementia group, low dose group and high dose group. The spatial cognition and memory of mice were measured by Morris water maze with different concentration of curcumin forage for 6 months. Serum total cholesterol (TC) and high density lipoprotein (HDL) were measured by cholesterol enzymatic colorimetry. The expression of A 尾 42 in transgenic brain tissue and the expression of; Realtime PCR and apoA1 in hippocampal CA1 pyramidal cells were detected by immunohistochemistry.; Realtime PCR and Western Blotting were used to detect the changes of mRNA and protein levels of LXR- 尾 RXR- 偽 and ABCA1 in brain tissue of transgenic mice. Results the results of the water maze test showed that the spatial cognition and memory ability of AD transgenic mice were significantly improved by curcumin feeding. The TC content in serum of AD transgenic mice was significantly decreased after curcumin feeding, while the content of HDL was increased in AD transgenic mice. The difference was statistically significant (P < 0.05). Immunohistochemical staining showed that the production of A 尾 42 in the brain tissue of mice in low dose and high dose groups was significantly decreased. The expression of LXR- 尾 RXR- 偽 CA1 and apoA1 in the hippocampus of transgenic mice was significantly higher than that in curcumin fed group and not fed curcumin group, and the expression of LXR- 尾 RXR- 偽 ABCA1 and apoA1 in hippocampus of transgenic mice was significantly higher than that in curcumin fed group. The protein expression in high dose group was significantly higher than that in low dose group, and the difference was statistically significant. The mRNA expression of LXR- 尾 RXR- 偽 and ABCA1 in the brain tissues of transgenic mice fed with curcumin was increased, and the corresponding protein expression was also increased. The difference was statistically significant. Conclusion the cholesterol transmembrane transport system of ABCA1 plays an important role in the development of Alzheimer's disease. Curcumin can improve the lipid metabolism of AD by enhancing the transmembrane transport of ABCA1 through LXR- 尾 and RXR- 偽.
【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】：2013
【分類號(hào)】：R749.16

【共引文獻(xiàn)】

相關(guān)博士學(xué)位論文 前1條

1 劉黎星;ABCA1在子癇前期發(fā)病中的作用及其機(jī)制研究[D];福建醫(yī)科大學(xué);2013年

相關(guān)碩士學(xué)位論文 前1條

1 周宗麗;三轉(zhuǎn)基因Alzheimer癥模型小鼠的社會(huì)行為學(xué)和一種新型M1受體激動(dòng)劑對(duì)該小鼠的影響[D];華東師范大學(xué);2013年

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本文編號(hào)：1947336