| 李峰,景洪江,李惠子,张新胜,徐庆,张永,薛长勇,刘英华.APP/PS1小鼠血脂与β-淀粉样蛋白、Tau蛋白表达水平的相关性及中链脂肪酸的干预作用[J].中华老年多器官疾病杂志,2022,21(10):766~770 |
| APP/PS1小鼠血脂与β-淀粉样蛋白、Tau蛋白表达水平的相关性及中链脂肪酸的干预作用 |
| Correlation of serum lipids with cerebral Aβ and Tau expression and intervention of mediumchain fatty acids in APP/PS1 mice |
| 投稿时间：2022-06-07 |
| DOI：10.11915/j.issn.1671-5403.2022.10.165 |
| 中文关键词: 阿尔茨海默症 中链脂肪酸 APP/PS1转基因小鼠 血脂 |
| 英文关键词:Alzheimer disease medium-chain fatty acid APP/PS1 transgenic mice serum lipids This work was supported by the National Natural Science Foundation of China |
| 基金项目:国家自然科学基金(81541067,81703204) |
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| 中文摘要: |
| 目的 探讨APP/PS1小鼠血脂与β-淀粉样蛋白(Aβ)、Tau蛋白表达水平的相关性及中链脂肪酸(MCFA)的干预作用,为MCFA防治阿尔兹海默症(AD)的相关机制提供理论依据。方法 将17只4周龄APP/PS1转基因小鼠随机分为中链脂肪酸组(MCFA组,9只)和长链脂肪酸组(LCFA组,8只),同窝阴性野生型小鼠9只作为野生型小鼠(WT)组。MCFA组和LCFA组小鼠用不同脂肪酸配制饲料连续喂养至36周龄,检测总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、Aβ前体蛋白(APP)、Aβ及Tau蛋白表达水平。采用SPSS 22.0统计软件进行数据分析。采用t检验进行计量资料组间比较。采用Pearson相关分析血脂与Aβ、Tau蛋白表达水平之间的相关性。结果 MCFA组小鼠TC、TG水平,大脑皮层和海马组织Aβ及Tau蛋白表达均明显低于LCFA组(P＜0.01)。相关性分析结果显示,TG与皮层组织Aβ蛋白表达水平呈正相关(r=0.399；P＜0.05)；而TC则与皮层和海马组织Aβ蛋白表达水平均呈显著正相关(r=0.715,0.748；P＜0.01),也与海马组织Tau蛋白表达水平呈正相关(r=0.603；P＜0.05)。结论 MCFA可能通过调节APP/PS1转基因小鼠脂代谢,特别是降低TC水平,减少大脑组织Aβ蛋白沉积及Tau蛋白磷酸化水平,从而发挥防治AD的作用。 |
| 英文摘要: |
| Objective To investigate the correlation between serum lipids and expression levels of β-Amyloid protein (Aβ) and Tau in brain, and determine the intervention effect of medium-chain fatty acid (MCFA) in APP/PS1 mice, so as to provide a theoretical basis for exploring the mechanism of MCFA in the prevention and treatment of Alzheimer′s disease (AD). Methods Seventeen 4-week-old APP/PS1 transgenic mice were randomly divided into MCFA group (n=9) and long-chain fatty acid (LCFA) group (n=8), and 9 littermates of negative wild-type mice served as wide type (WT) group. Mice in each group were fed with diets prepared by different fatty acids until they were 36 weeks old, then the blood samples were collected to measure the serum lipids, including total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and the brain tissues were harvested to detect the expression levels of Aβ precursor protein (APP), Aβ and Tau protein in the cerebral cortex and hippocampus. SPSS statistics 22.0 was used for statistical analysis. Data comparison between the two groups was performed using student′s t test for measurement data. Pearson correlation analysis was used to analyze the correlation between blood lipids and the protein levels of Aβ and Tau. Results The serum levels of TC and TG and the protein levels of Aβ and Tau in the cerebral cortex and hippocampus were significantly lower in the MCFA group than the LCFA group (P<0.01). Correlation analysis indicated that serum TG was positively correlated with the Aβ level in the cortex(r=0.399; P<0.05), while serum TC was positively correlated with the expression level of Aβ in both cortex and hippocampus (r=0.715,0.748; P<0.01), and with the expression level of Tau in the hippocampus (r=0.603; P<0.05). Conclusion MCFA reduces Aβ deposition and Tau phosphorylation in the brain probably through regulating lipid metabolism, especially decreasing TC level in APP/PS1 transgenic mice, and thus plays a role in the prevention and treatment of AD. |
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