Kim Christine H J, Mitchell James B, Bursill Christina A, Sowers Anastasia L, Thetford Angela, Cook John A, van Reyk David M, Davies Michael J
Free Radical Group, Heart Research Institute, 7 Eliza Street, Newtown, NSW 2042, Australia; Faculty of Medicine, University of Sydney, NSW 2006, Australia.
National Cancer Institute, Radiation Biology Branch, Center for Cancer Research, Building 10, Room B3-B69, Bethesda, MD 20892, USA.
Atherosclerosis. 2015 May;240(1):234-41. doi: 10.1016/j.atherosclerosis.2015.03.012. Epub 2015 Mar 16.
The nitroxide compound TEMPOL (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl radical) has been shown to prevent obesity-induced changes in adipokines in cell and animal systems. In this study we investigated whether supplementation with TEMPOL inhibits inflammation and atherosclerosis in apoE-/- mice fed a high fat diet (HFD).
ApoE-/- mice were fed for 12 weeks on standard chow diet or a high-fat diet. Half the mice were supplemented with 10 mg/g TEMPOL in their food. Plasma samples were analysed for triglycerides, cholesterol, low- and high-density lipoprotein cholesterol, inflammatory cytokines and markers (interleukin-6, IL-6; monocyte-chemotactic protein, MCP-1; myeloperoxidase, MPO; serum amyloid A, SAA; adiponectin; leptin). Plaques in the aortic sinus were analysed for area, and content of collagen, lipid, macrophages and smooth muscle cells.
High fat feeding resulted in marked increases in body mass and plasma lipid levels. Dietary TEMPOL decreased both parameters. In the high-fat-fed mice significant elevations in plasma lipid levels and the inflammatory markers IL-6, MCP-1, MPO, SAA were detected, along with an increase in leptin and a decrease in adiponectin. TEMPOL supplementation reversed these effects. When compared to HFD-fed mice, TEMPOL supplementation increased plaque collagen content, decreased lipid content and increased macrophage numbers.
These data indicate that in a well-established model of obesity-associated hyperlipidaemia and atherosclerosis, TEMPOL had a significant impact on body mass, atherosclerosis, hyperlipidaemia and inflammation. TEMPOL may therefore be of value in suppressing obesity, metabolic disorders and increasing atherosclerotic plaque stability.
氮氧化物化合物TEMPOL（4-羟基-2,2,6,6-四甲基哌啶-N-氧基自由基）已被证明可在细胞和动物系统中预防肥胖引起的脂肪因子变化。在本研究中，我们调查了补充TEMPOL是否能抑制喂食高脂饮食（HFD）的载脂蛋白E基因敲除（apoE-/-）小鼠的炎症和动脉粥样硬化。
将apoE-/-小鼠分别用标准饲料或高脂饲料喂养12周。一半的小鼠在食物中补充10 mg/g的TEMPOL。分析血浆样本中的甘油三酯、胆固醇、低密度和高密度脂蛋白胆固醇、炎性细胞因子和标志物（白细胞介素-6，IL-6；单核细胞趋化蛋白，MCP-1；髓过氧化物酶，MPO；血清淀粉样蛋白A，SAA；脂联素；瘦素）。分析主动脉窦中的斑块面积以及胶原蛋白、脂质、巨噬细胞和平滑肌细胞的含量。
高脂喂养导致体重和血浆脂质水平显著增加。饮食中补充TEMPOL可降低这两个参数。在喂食高脂饲料的小鼠中，检测到血浆脂质水平以及炎性标志物IL-6、MCP-1、MPO、SAA显著升高，同时瘦素增加而脂联素减少。补充TEMPOL可逆转这些作用。与喂食高脂饲料的小鼠相比，补充TEMPOL可增加斑块胶原蛋白含量，降低脂质含量并增加巨噬细胞数量。
这些数据表明，在一个成熟的肥胖相关高脂血症和动脉粥样硬化模型中，TEMPOL对体重、动脉粥样硬化、高脂血症和炎症有显著影响。因此，TEMPOL在抑制肥胖、代谢紊乱和增加动脉粥样硬化斑块稳定性方面可能具有价值。
