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矢车菊素-3-葡萄糖苷对APPswe/PS1ΔE9阿尔茨海默病模型小鼠糖脂代谢的影响

宋楠 张玲 陈巍 张倩 韩云林 秦川

中国比较医学杂志2016,Vol.26Issue(7):15-23,9.
中国比较医学杂志2016,Vol.26Issue(7):15-23,9.DOI:10.3969.j.issn.1671-7856.2016.07.003

矢车菊素-3-葡萄糖苷对APPswe/PS1ΔE9阿尔茨海默病模型小鼠糖脂代谢的影响

Effect of cyaniding-3-glucoside on glucose and lipid metabolism in the APP swe/PS1ΔE9 mouse model of Alzheimer̓s disease

宋楠 1张玲 1陈巍 1张倩 1韩云林 1秦川1

作者信息

  • 1. 北京协和医学院比较医学中心,中国医学科学院医学实验动物研究所,卫生部人类疾病比较医学重点实验室,北京 100021
  • 折叠

摘要

Abstract

Objective To investigate the effect of cyaniding⁃3⁃glucoside (Cy3G) on glucose and lipid metabolism in the APPswe/PS1ΔE9 mouse model of Alzheimer’s disease (AD). Methods Seven⁃month⁃old APPswe/PS1ΔE9(PAP) mice were randomly divided into model group (PAP), Cy3G treatment group (PAPCy, 5 mg/kg/d) and negative⁃control group (nPAP). In addition, age⁃matched and normal wild⁃type of C57BL/6J mice were selected and divided into vehicle group (WT), Cy3G intervention group (WTCy, 5 mg/kg/d). Each group containing 12 mice, with equal number of male and female mice. After 8⁃week Cy3G supplementation, microPET/CT was used to measure cerebral glucose metabolism rate of mice in each group. Biochemical methods were used to detect the liver / kidney function as well as indicators associated with lipid metabolism. After weighting brain tissue, the brain coefficient was tested and pathological examination was used to observe tissues changes. Transmission electron microscope was used to observe neuropathological amyloid plaques deposition. Western⁃blot was used to determine protein levels of AKT and JNK. Results Compared with the WT group, PAP mice had low levels of 18 F⁃FDG uptake rates, especially in the regions of the frontal lobe and hippocampus accompanied by the decreased brain coefficient and amyloid plaques deposition in hippocampus. And levels of aspartate transaminase ( AST) and lactic dehydrogenase ( LDH) were also increased in PAP mice, but lipid metabolism index was relatively normal. In addition, the expression of JNK was decreased and AKT was increased in mice of PAP. However, in the PAPCy group, 18 F⁃FDG uptake rates were obviously increased in the regions of the frontal lobe and hippocampus compared with those in the PAP mice. And the reduction of brain atrophy and amyloid plaques deposition, normal lipid metabolism and no obvious liver/kidney toxicity were also observed. Cy3G also could reverse the changes of JNK and AKT protein. Conclusions Cy3G can improve glucose metabolism disorders instead of lipid metabolism, inhibit the senile plaques deposition in hippocampus and regulate insulin resistance and inflammatory reaction associated with JNK/AKT pathway. Thus, Cy3G has a good safety profile and may be used as an ideal alternative to traditional disease⁃modifying treatments against AD.

关键词

阿尔茨海默病/矢车菊素-3-葡萄糖苷/葡脂代谢

Key words

Alzheimer̓s disease/Cyaniding-3-glucoside/Glucose and lipid metabolism

分类

医药卫生

引用本文复制引用

宋楠,张玲,陈巍,张倩,韩云林,秦川..矢车菊素-3-葡萄糖苷对APPswe/PS1ΔE9阿尔茨海默病模型小鼠糖脂代谢的影响[J].中国比较医学杂志,2016,26(7):15-23,9.

基金项目

国家自然基金(81500938);协和青年基金(3332015151)。 ()

中国比较医学杂志

OA北大核心CSTPCD

1671-7856

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