Effect of Dehydroepiandrosterone on Atherosclerosis in Apolipoprotein E-Deficient Mice

脱氢表雄酮对载脂蛋白 E 缺陷小鼠动脉粥样硬化的影响

• 批准号: 18590820
• 负责人: YAMAKAWA Tadashi
• 金额: $ 2.43万
• 依托单位: YOKOHAMA CITY UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590820/
• 关键词: dehydroepiandrosterone; atherosclerosis; monocyte chemoattractant protein-1; macrophage; apolipoportein E-knockout mice; MCP-1; DHEA-S; ApoE; サイトカイン

Aim : Several clinical trials have indicated that dehydroepiandrosterone (DHEA) reduces coronary events associated with atherosclerosis. The aim of this study was to examine the inhibitory effect of DHEA on atherosclerosis and the mechanisms involved. Methods : Apolipoprotein E-knockout (apoE-KO) mice were fed an atherogenic high-cholesterol diet with or without 0.4% (w/w) DHEA for 12 weeks.Results : Although the plasma cholesterol and triglyceride levels were not decreased by DHEA. atherosclerotic lesions in the aortic sinus showed a 45% reduction in area with DHEA treatment versus untreated mice. Accumulation of macrophages in aortic lesions was also markedly reduced in the DHEA group. Furthermore. DHEA suppressed the expression of monocyte chemoattractant protein-1 in the vessel wall. Thus, inhibition of macrophage infiltration by DHEA reduced the formation of atherosclerotic lesions in apoE-KO mice.Conclusions : DHEA might be an effective agent for clinical management of atherosclerosis, but a larger controlled trial is necessary for confirmation.

目的：多项临床试验表明，脱氢表雄酮 (DHEA) 可减少与动脉粥样硬化相关的冠状动脉事件。本研究的目的是探讨 DHEA 对动脉粥样硬化的抑制作用及其机制。方法：载脂蛋白 E 敲除 (apoE-KO) 小鼠喂食致动脉粥样硬化的高胆固醇饮食，含或不含 0.4% (w/w) DHEA，持续 12 周。 结果：尽管 DHEA 并未降低血浆胆固醇和甘油三酯水平。与未治疗的小鼠相比，接受 DHEA 治疗的小鼠主动脉窦动脉粥样硬化病变面积减少了 45%。 DHEA 组主动脉病变中巨噬细胞的积累也显着减少。此外。 DHEA 抑制血管壁中单核细胞趋化蛋白-1 的表达。因此，DHEA抑制巨噬细胞浸润可减少apoE-KO小鼠动脉粥样硬化病变的形成。结论：DHEA可能是动脉粥样硬化临床治疗的有效药物，但需要更大规模的对照试验来证实。

项目成果

DHEAの抗動脈硬化作用とその機序について

关于DHEA的抗动脉硬化作用及其机制

• 发表时间: 2009
• 作者: Ehara S;Yoshiyama M.;山川正
• 通讯作者: 山川正