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载脂蛋白 E 基因敲除小鼠脑内胆固醇含量、合成速率和输出减少。

Decreased content, rate of synthesis and export of cholesterol in the brain of apoE knockout mice.

机构信息

Laboratorio de Lipides, LIM-10, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, Av. Dr. Arnaldo, 455 - room 3305, São Paulo, SP, CEP 01246-000, Brazil.

出版信息

J Bioenerg Biomembr. 2018 Aug;50(4):283-287. doi: 10.1007/s10863-018-9757-9. Epub 2018 Apr 20.

DOI:10.1007/s10863-018-9757-9
PMID:29675736
Abstract

Apolipoprotein E knockout (apoE-KO) mice present synaptic loss, cognitive dysfunction, and high plasma lipid levels that may affect brain function simulating Alzheimer disease. Plasma and brain sterols were measured in apoE-KO and in wild type control mice on a cholesterol-free, phytosterol-containing diet by gas chromatography coupled to a mass spectrometer. Plasma cholesterol and phytosterols (campesterol and sitosterol) were higher in apoE-KO compared to control mice. Cholesterol precursors (desmosterol and lathosterol) were not detected in plasma of control mice but were present in apoE-KO mice. In the brain amounts of cholesterol, desmosterol, campesterol and 24-hydroxycholesterol were significantly lower in apoE-KO than in controls. There is a tendency in apoE-KO for lower values of 7α-hydroxycholesterol and 7β-hydroxycholesterol. Cholesterol content, synthesis rates (desmosterol) and export of 24-hydroxycholesterol are reduced in the brain of the severe hypercholesterolemic apoE-KO mice.

摘要

载脂蛋白 E 基因敲除(apoE-KO)小鼠表现出突触丧失、认知功能障碍和高血浆脂质水平,这些可能模拟阿尔茨海默病影响大脑功能。通过气相色谱-质谱联用仪测量了无胆固醇、含植物固醇饮食的 apoE-KO 和野生型对照小鼠的血浆和脑固醇。与对照组相比,apoE-KO 小鼠的血浆胆固醇和植物固醇(菜油固醇和谷固醇)水平更高。胆固醇前体(羊毛固醇和麦角固醇)在对照组的血浆中未被检测到,但在 apoE-KO 小鼠中存在。在大脑中,apoE-KO 小鼠的胆固醇、羊毛固醇、菜油固醇和 24-羟基胆固醇含量明显低于对照组。apoE-KO 小鼠的 7α-羟基胆固醇和 7β-羟基胆固醇值呈降低趋势。严重高胆固醇血症 apoE-KO 小鼠的大脑中胆固醇含量、合成率(羊毛固醇)和 24-羟基胆固醇的输出减少。

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