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红花黄色素对 APP/PS1 小鼠血清和脑组织中胆固醇水平的影响。

Effects of safflower yellow on cholesterol levels in serum and brain tissue of APP/PS1 mice.

机构信息

Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, Department of Pharmacology, Shihezi University, Shihezi, Xinjiang, 832000, People's Republic of China.

出版信息

Metab Brain Dis. 2021 Apr;36(4):557-569. doi: 10.1007/s11011-021-00680-0. Epub 2021 Feb 6.

Abstract

Alzheimer's disease (AD) is an aggressive neurodegenerative disease associated with cognitive decline, memory, language, and visual-spatial coordination disorders that eventually lead to complete loss of basic function. Hypercholesterolemia plays an important role in the pathogenesis of AD and its related diseases. Safflower yellow (SY) is a natural chalcone compound isolated from safflower, which has the effect of antioxidation and weight loss. Previous studies have shown that SY has a significant improvement in learning and memory in various AD model animals. In the early stage of proteomic technology, we found that the cholesterol synthesis rate-limiting enzyme Mevalonate decarboxylase (MVD) was abnormally high in dementia rats, and the expression level of MVD decreased after SY treatment. We speculated that SY may improve the learning and memory ability of AD mice by affecting cholesterol metabolism. The purpose of this study was to evaluate the effect of SY on regulating cholesterol metabolism and improving dementia. The area of amyloid-β (Aβ) plaque in the brain of APP/PS1 mice and various blood biochemical and molecular biological indexes was detected. Through behavioral experiments, we found that APP/ PS1 mice had significant learning and memory impairment compared with wild type mice(P < 0.01). SY (30 mg/kg) treatment for 1 month can significantly improve the learning and memory ability of APP/PS1 mice (P < 0.01). Our results showed that SY decreased serum Total cholesterol (TC) and Triglyceride (TG) and increased the level of High-density lipoprotein (HDL). HE staining obscured that SY affect the changes of liver tissue in APP/PS1 mice (P < 0.05 and P < 0.01). We found that SY reduced the expression of MVD and Apolipoprotein E (APOE4) in the cortex (P < 0.05 and P < 0.01). In summary, SY can effectively control cholesterol in serum and brain and change the degeneration of liver tissue. SY improves Alzheimer's disease by lowering serum, cortex and cortical cholesterol.

摘要

阿尔茨海默病(AD)是一种侵袭性神经退行性疾病,与认知能力下降、记忆力、语言和视觉空间协调障碍有关,最终导致基本功能完全丧失。高胆固醇血症在 AD 及其相关疾病的发病机制中起着重要作用。红花黄色素(SY)是从红花中分离出来的天然查尔酮化合物,具有抗氧化和减肥的作用。先前的研究表明,SY 对各种 AD 模型动物的学习和记忆有显著改善作用。在蛋白质组学技术的早期,我们发现痴呆症大鼠的胆固醇合成限速酶甲羟戊酸脱羧酶(MVD)异常升高,SY 治疗后 MVD 的表达水平降低。我们推测 SY 可能通过影响胆固醇代谢来改善 AD 小鼠的学习和记忆能力。本研究旨在评价 SY 调节胆固醇代谢和改善痴呆的作用。检测了 APP/PS1 小鼠脑内淀粉样-β(Aβ)斑块面积及各项血液生化和分子生物学指标。通过行为学实验,我们发现 APP/PS1 小鼠与野生型小鼠相比,学习和记忆能力显著受损(P < 0.01)。SY(30 mg/kg)治疗 1 个月可显著改善 APP/PS1 小鼠的学习和记忆能力(P < 0.01)。结果表明,SY 降低了血清总胆固醇(TC)和甘油三酯(TG)水平,增加了高密度脂蛋白(HDL)水平。HE 染色表明 SY 影响 APP/PS1 小鼠肝脏组织的变化(P < 0.05 和 P < 0.01)。我们发现 SY 降低了皮质中 MVD 和载脂蛋白 E(APOE4)的表达(P < 0.05 和 P < 0.01)。综上所述,SY 能有效控制血清和脑组织中的胆固醇,改变肝脏组织的退化。SY 通过降低血清、皮质和皮质胆固醇来改善阿尔茨海默病。

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