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DHA 膳食干预导致载脂蛋白 E 基因敲除小鼠和 C57BL/6J 小鼠的海马脂质和蛋白质图谱存在差异。

DHA dietary intervention caused different hippocampal lipid and protein profile in ApoE-/- and C57BL/6J mice.

机构信息

School of Public Health, Capital Medical University, Beijing, China; China-British Joint Laboratory of Nutrition Prevention and Control of Chronic Diseases.

School of Public Health, Capital Medical University, Beijing, China.

出版信息

Biomed Pharmacother. 2024 Aug;177:117088. doi: 10.1016/j.biopha.2024.117088. Epub 2024 Jul 6.

Abstract

BACKGROUND

Changes in protein and lipid levels may occur in the Alzheimer's disease brain, and DHA can have beneficial effects on it. To investigate the impact of DHA dietary intervention on brain protein and lipid profile in ApoE-/- mice and C57 mice.

METHOD

Three-month-old ApoE-/- mice and C57 mice were randomly divided into two groups respectively, and fed with control diet and DHA-fortified diet for five months. Cortical TC, HDL-C and LDL-C levels and cholesterol metabolism-related protein expression were measured by ELISA or immunohistochemistry methods. Hippocampus were collected for proteomic and lipidomics analysis by LC-MS/MS and differential proteins and lipid metabolites were screened and further analyzed by GO functional annotation and KEGG pathway enrichment analysis.

RESULTS

DHA intervention decreased cortical TC level in both C57 and ApoE-/- mice (P < 0.05), but caused different change of cortical HDL-C, LDL-C level and LDL-C/HDL-C ratio in C57 and ApoE-/- mice (P < 0.05). Discrepant cortical and hippocampal LDLR, ABCG1, Lox1 and SORT1 protein expression was found between C57 and ApoE-/- mice (P < 0.05), and DHA treatment caused different changes of these proteins in C57 and ApoE-/- mice (P < 0.05). Differential hippocampal proteins and lipids profile were found in C57 and ApoE-/- mice before and after DHA treatment, which were mainly involved in vesicular transport and phospholipid metabolic pathways.

CONCLUSION

ApoE genetic defect caused abnormal cholesterol metabolism, and affected protein and lipid profile, as well as discrepant response of hippocampal protein and lipids profile in the brain of mice given DHA fortified diet intervention.

摘要

背景

阿尔茨海默病大脑中可能会发生蛋白质和脂质水平的变化,而 DHA 对其可能有有益影响。本研究旨在探讨 DHA 饮食干预对 ApoE-/-小鼠和 C57 小鼠大脑蛋白质和脂质谱的影响。

方法

将 3 月龄 ApoE-/-小鼠和 C57 小鼠随机分为两组,分别给予对照饮食和富含 DHA 的饮食,干预 5 个月。通过 ELISA 或免疫组化方法检测皮质 TC、HDL-C 和 LDL-C 水平及胆固醇代谢相关蛋白的表达。通过 LC-MS/MS 收集海马组织进行蛋白质组学和脂质组学分析,筛选差异蛋白质和脂质代谢物,并进一步进行 GO 功能注释和 KEGG 通路富集分析。

结果

DHA 干预降低了 C57 和 ApoE-/-小鼠皮质 TC 水平(P<0.05),但对 C57 和 ApoE-/-小鼠皮质 HDL-C、LDL-C 水平及 LDL-C/HDL-C 比值的影响不同(P<0.05)。C57 和 ApoE-/-小鼠皮质 LDLR、ABCG1、Lox1 和 SORT1 蛋白表达存在差异(P<0.05),DHA 处理导致 C57 和 ApoE-/-小鼠这些蛋白表达不同(P<0.05)。DHA 处理前后,C57 和 ApoE-/-小鼠的海马差异蛋白质和脂质谱不同,主要涉及囊泡运输和磷脂代谢途径。

结论

ApoE 遗传缺陷导致胆固醇代谢异常,并影响大脑中蛋白质和脂质谱,以及富含 DHA 的饮食干预对小鼠海马蛋白和脂质谱的不同反应。

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