Swimming reduces the severity of atherosclerosis in apolipoprotein E deficient mice by antioxidant effects
Swimming reduces the severity of atherosclerosis in apolipoprotein E deficient mice by antioxidant effects
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DOI：
10.1016/j.cardiores.2007.02.019
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发表时间：
2007-06-01
影响因子：
10.8
通讯作者：
Kishimoto, Chiharu
中科院分区：
文献类型：
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作者：
Okabe, Taka-aki;Shimada, Kana;Kishimoto, Chiharu
目的：有氧运动训练可预防动脉粥样硬化的发展。然而，确切的机制仍然未知。我们评估的假设，运动训练降低了实验性动脉粥样硬化的严重程度载脂蛋白（载脂蛋白）E-缺陷小鼠的抗氧化effics.Methods：运动训练（45分钟游泳，3次/周）进行了载脂蛋白E-缺陷小鼠高脂饮食。在8周和16周内，隔日对小鼠进行运动和不运动治疗，另外的运动治疗小鼠口服25 mg/kg/天的N-G-硝基-L-精氨酸甲酯（L-NAME），一种一氧化氮合酶（NOS）抑制剂。结果：高脂饲料喂养的apo E基因缺陷小鼠在8周时出现脂肪条纹形成，16周时出现纤维脂肪斑块，而游泳训练8周和16周的小鼠脂肪条纹形成和纤维脂肪斑块形成均受到抑制。与此相反，动脉粥样硬化病变并没有改善与口服L-NAME相关的运动训练治疗的小鼠。然而，在与L-NAME和L-精氨酸相关的游泳治疗的小鼠中，动脉粥样硬化病变减少。免疫组织化学分析显示，在运动治疗的小鼠中，脂肪条纹病变中的巨噬细胞和CD 4（+）细胞积聚受到抑制，但在与L-NAME给药相关的运动治疗中则没有。动脉粥样硬化病变的严重程度与内皮NOS表达和内源性抗氧化蛋白硫氧还蛋白的表达呈负相关。也就是说，与没有运动的小鼠相比，运动处理的小鼠中硫氧还蛋白的表达受到抑制。血浆硫代巴比妥酸反应物质水平显着低于运动组比那些没有运动或运动与L-NAME管理，这表明运动引起的脂质过氧化反应较少。病变面积的差异与血脂水平的任何显著变化无关。在本研究中使用的运动负荷并没有影响能量代谢efficaciesin the hearts.Conclusion：运动训练，其中的负荷并没有影响能量代谢效率的心脏，抑制动脉粥样硬化的抗氧化作用，通过血管NO系统。(C)2007年欧洲心脏病学会。Elsevier B. V.出版，保留所有权利。
Objective: It was shown that aerobic exercise training may protect against the development of atherosclerosis. However, the precise mechanisms are still unknown. We assessed the hypothesis that exercise training reduced the severity of experimental atherosclerosis in apolipoprotein (apo) E-deficient mice by antioxidant effects.Methods: Exercise training (45 min swimming, 3 times/week) was conducted on apo E-deficient mice fed a high fat diet. Over 8 and 16 weeks on alternate days, mice were treated with and without exercise, and additional exercise-treated mice were orally given 25 mg/kg/day of N-G-nitro-L-arginine methylester (L-NAME), an inhibitor of nitric oxide synthase (NOS). In addition, the effect of L-arginine against L-NAME was also tested.Results: Fatty streak formation at 8 weeks and fibrofatty plaques at 16 weeks developed in apo E-deficient mice fed a high fat diet, and were suppressed in mice treated with swimming for 8 and 16 weeks. In contrast, atherosclerotic lesions were not ameliorated in mice treated with exercise training associated with oral L-NAME. However, in mice treated with swimming associated with L-NAME and L-arginine, the atherosclerotic lesions were reduced. Immunohistochemical analysis revealed that macrophage and CD4(+) cell accumulation in the fatty streak lesions was suppressed in mice treated with exercise, but not in those treated with exercise associated with L-NAME administration. The severity of atherosclerotic lesions was inversely correlated with the endothelial NOS expression and the expression of an endogenous antioxidant protein, thioredoxin. Namely, the expression of thioredoxin in mice treated with exercise was suppressed compared with mice without exercise. Plasma thiobarbituric acid-reactive substance levels were significantly lower in groups with exercise than in those without exercise or with exercise associated with L-NAME administration, suggesting exercise-induced less lipid peroxidation. Differences in lesion area did not correlate with any significant alterations in serum lipid levels. The exercise load used in the current study did not affect energy metabolism efficacies in the hearts.Conclusion: Exercise training, in which the load did not affect energy metabolism efficacy of the heart, suppressed atherosclerosis by antioxidant effects via the vascular NO system. (C) 2007 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.