Effect of Dehydroepiandrosterone on Atherosclerosis in Apolipoprotein E-Deficient Mice

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。本研究旨在探讨脱氢表雄酮对动脉粥样硬化的抑制作用及其机制。方法：用含或不含0.4%(w/w)DHEA的高脂饲料喂养载脂蛋白E基因敲除(apoE-KO)小鼠12周。结果：DHEA不降低血浆胆固醇和甘油三酯水平。与未治疗的小鼠相比，DHEA治疗后，主动脉窦动脉粥样硬化病变的面积减少了45%。DHEA组大鼠主动脉病变内巨噬细胞积聚也明显减少。更重要的是。DHEA抑制血管壁单核细胞趋化蛋白-1的表达。结论：脱氢表雄酮可能是一种有效的治疗动脉粥样硬化的药物，但需要进行更大规模的对照试验才能得到证实。

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.