Shing Cecilia M, Fassett Robert G, Peake Jonathan M, Coombes Jeff S
School of Health Sciences, University of Tasmania, Launceston, Tas., Australia.
Cardiovasc Ther. 2014 Dec;32(6):270-5. doi: 10.1111/1755-5922.12096.
BACKGROUND/AIMS: Inflammation and endothelial dysfunction contribute to cardiovascular disease, prevalent in chronic kidney disease (CKD). Antioxidant supplements such as tocopherols may reduce inflammation and atherosclerosis. This study aimed to investigate the effect of tocopherol supplementation on vascular function, aortic plaque formation, and inflammation in apolipoprotein E(-/-) mice with 5/6 nephrectomy as a model of combined cardiovascular and kidney disease.
Nephrectomized mice were assigned to a normal chow diet group (normal chow), a group receiving 1000 mg/kg diet of α-tocopherol supplementation or a group receiving 1000 mg/kg diet mixed-tocopherol (60% γ-tocopherol).
Following 12 weeks, in vitro aortic endothelial-independent relaxation was enhanced with both α-tocopherol and mixed-tocopherol (P < 0.05), while mixed-tocopherol enhanced aortic contraction at noradrenaline concentrations of 3 × 10(-7) M to 3 × 10(-5) M (P < 0.05), when compared to normal chow. Supplementation with α- and mixed-tocopherol reduced systemic concentrations of IL-6 (P < 0.001 and P < 0.001, respectively) and IL-10 (P < 0.05 and P < 0.001, respectively), while α-tocopherol also reduced MCP-1 (P < 0.05) and tumor necrosis factor (TNF)-α (P < 0.05). Aortic sinus plaque area was significantly reduced with α-tocopherol supplementation when compared to normal chow (P < 0.01).
Tocopherol supplementation favorably influenced vascular function and cytokine profile, while it was also effective in reducing atherosclerosis in the apolipoprotein E(-/-) mouse with CKD.
背景/目的：炎症和内皮功能障碍与心血管疾病相关，在慢性肾脏病（CKD）中很常见。抗氧化剂补充剂如生育酚可能会减轻炎症和动脉粥样硬化。本研究旨在以5/6肾切除的载脂蛋白E基因敲除（ApoE-/-）小鼠作为合并心血管和肾脏疾病的模型，探讨补充生育酚对血管功能、主动脉斑块形成和炎症的影响。
将肾切除小鼠分为正常饲料组（正常饲料）、接受1000 mg/kg饲料α-生育酚补充剂的组或接受1000 mg/kg饲料混合生育酚（60%γ-生育酚）的组。
12周后，与正常饲料组相比，α-生育酚和混合生育酚均增强了体外主动脉非内皮依赖性舒张（P<0.05），而混合生育酚在去甲肾上腺素浓度为3×10-7 M至3×10-5 M时增强了主动脉收缩（P<0.05）。补充α-生育酚和混合生育酚降低了全身IL-6浓度（分别为P<0.001和P<0.001）和IL-10浓度（分别为P<0.05和P<0.001），而α-生育酚还降低了MCP-1（P<0.05）和肿瘤坏死因子（TNF）-α（P<0.05）。与正常饲料组相比，补充α-生育酚显著减少了主动脉窦斑块面积（P<0.01）。
补充生育酚对血管功能和细胞因子谱有有利影响，同时对患有CKD的ApoE-/-小鼠减少动脉粥样硬化也有效。
