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Aged Garlic Extract Suppresses the Development of Atherosclerosis in Apolipoprotein E-Knockout Mice.
作者信息
Morihara Naoaki, Hino Atsuko, Yamaguchi Takako, Suzuki Jun-Ichiro
机构信息
Drug Discovery Laboratory and
Healthcare Research and Development Division, Wakunaga Pharmaceutical Co., Ltd., Akitakata, Japan.
出版信息
J Nutr. 2016 Feb;146(2):460S-463S. doi: 10.3945/jn.114.206953. Epub 2016 Jan 13.
BACKGROUND
Aged garlic extract (AGE) has been shown to retard the progression of coronary calcification in patients with coronary artery disease.
OBJECTIVE
To clarify the mechanism of AGE's action to retard atherosclerosis, we investigated whether AGE suppresses the formation and progression of atherosclerosis in Apolipoprotein E (Apoe)-knockout (ApoE-KO) mice.
METHODS
Male C57BL/6J mice (control mice, 5 wk old) were fed a standard diet, whereas male ApoE-KO mice (5 wk old) were fed a standard diet with or without 3% AGE for 12 or 24 wk. After the treatment, blood samples, aortas, and spleens were collected from all mice. Concentrations of total cholesterol (TC), HDL cholesterol, and triglycerides (TGs) in serum were measured. The area of atherosclerotic lesion in the aorta was examined by Oil Red O staining. The relative abundances of monocytes plus macrophages (CD11b(+) cells) and interferon-γ-producing CD4(+) T cells in spleen were assessed by flow cytometric analysis.
RESULTS
The atherosclerotic lesion areas in the aortas of ApoE-KO mice were 87 and 114 times as great (P < 0.01) as those in control mice at 12 and 24 wk, respectively. AGE feeding significantly inhibited the progression of atherosclerotic lesion area in ApoE-KO mice by 22% (P < 0.05) at 12 wk. In addition, serum concentrations of TC and TGs in ApoE-KO mice were significantly higher than those in control mice at 12 and 24 wk. Treatment with AGE significantly suppressed the increases in serum concentrations of TC and TGs in ApoE-KO mice by 21% (P < 0.05) and 19% (P < 0.05) at 24 wk, respectively, and reduced the relative abundance of CD11b(+) cells in ApoE-KO mice by 24% (P < 0.05) at 12 wk.
CONCLUSION
These data suggest that the antiatherosclerotic activity of AGE is at least partly due to the suppression of inflammation and lipid deposition in the vessels during the early stage of atherosclerotic development in ApoE-KO mice.
背景
已有研究表明， aged garlic extract (AGE) 可延缓冠心病患者冠状动脉钙化的进展。
目的
为阐明AGE延缓动脉粥样硬化作用的机制，我们研究了AGE是否能抑制载脂蛋白E (Apoe) 基因敲除 (ApoE-KO) 小鼠动脉粥样硬化的形成和进展。
方法
雄性C57BL/6J小鼠（对照小鼠，5周龄）喂食标准饮食，而雄性ApoE-KO小鼠（5周龄）喂食含或不含3% AGE的标准饮食，持续12周或24周。处理后，采集所有小鼠的血液样本、主动脉和脾脏。测定血清中总胆固醇 (TC)、高密度脂蛋白胆固醇和甘油三酯 (TGs) 的浓度。通过油红O染色检查主动脉粥样硬化病变面积。通过流式细胞术分析评估脾脏中单核细胞加巨噬细胞 (CD11b(+) 细胞) 和产生干扰素-γ的CD4(+) T细胞的相对丰度。
结果
ApoE-KO小鼠主动脉粥样硬化病变面积在12周和24周时分别是对照小鼠的87倍和114倍（P < 0.01）。喂食AGE在12周时显著抑制了ApoE-KO小鼠动脉粥样硬化病变面积的进展，抑制率为22%（P < 0.05）。此外，ApoE-KO小鼠血清中TC和TGs浓度在12周和24周时显著高于对照小鼠。在24周时，用AGE处理分别显著抑制了ApoE-KO小鼠血清中TC和TGs浓度的升高，抑制率分别为21%（P < 0.05）和19%（P < 0.05），并在12周时使ApoE-KO小鼠中CD11b(+) 细胞的相对丰度降低了24%（P < 0.05）。
结论
这些数据表明，AGE的抗动脉粥样硬化活性至少部分归因于在ApoE-KO小鼠动脉粥样硬化发展早期对血管炎症和脂质沉积的抑制。
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