姜黄素通过ABCA1跨膜转运体系改善AD脂代谢紊乱的机制研究

发布时间：2018-05-28 16:03

本文选题：姜黄素 + 阿尔茨海默病　；参考：《重庆医科大学》2013年硕士论文

【摘要】：目的：脂代谢紊乱尤其是胆固醇代谢紊乱不仅是冠心病的致病因素，同样也是阿尔茨海默病（AD）的重要危险因素。大量研究已经证实，脑胆固醇代谢异常促进了AD的进展。姜黄素具有降低血脂的作用，但其机制仍不明确。本文主要探讨姜黄素通过影响三磷酸腺苷结合盒转运子A1（ABCA1）跨膜转运体系改善AD转基因小鼠脂代谢紊乱的机制。方法：APP/PS1双转基因小鼠Tg2576模型分三组，即痴呆组、低剂量组和高剂量组，不同浓度姜黄素饲料喂养6个月；Morris水迷宫检测各组小鼠空间认知和记忆能力的变化；胆固醇酶法比色法检测各组血清中总胆固醇（TC）和高密度脂蛋白（HDL）的含量；免疫组化检测各组转基因鼠脑组织Aβ42的表达情况以及海马CA1区锥体细胞的LXR-β、RXR-α、ABCA1和apoA1的表达情况； Realtime PCR和Western Blotting检测各组转基因小鼠脑组织LXR-β、RXR-α、ABCA1的mRNA和蛋白水平的变化。结果：Morris水迷宫实验结果表明AD转基因小鼠的空间认知和记忆能力经姜黄素喂养后明显改善。AD转基因小鼠经过姜黄素饲喂后血清中TC含量明显下降，而HDL的含量增高，其差异具有统计学意义（P㩳0.05）。免疫组织化学染色显示低剂量组和高剂量组小鼠的脑组织中Aβ42的生成明显减少，转基因小鼠脑组织海马CA1区的LXR-β、RXR-α、ABCA1和apoA1的表达在姜黄素饲喂组中明显高于未饲喂姜黄素组，且高剂量组的蛋白表达显著高于低剂量组的表达，其差异有统计学意义（P㩳0.05）。经过姜黄素饲喂的转基因小鼠的脑组织中LXR-β、RXR-α和ABCA1的mRNA表达增加而且相应的蛋白表达量也随之增加，其差异有统计学意义（P㩳0.05）。结论：ABCA1跨膜转运胆固醇体系在阿尔茨海默病的发生发展过程中有着重要的作用，姜黄素改善AD脂代谢紊乱可能与通过LXR-β和RXR-α增强ABCA1跨膜转运有关。
[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- 伪 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- 伪 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- 伪 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- 伪 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- 伪.
【学位授予单位】：重庆医科大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R749.16

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