AS (动脉粥样硬化)是一种大动脉管壁的病理改变状态。随着人民生活水平的提高，以及饮食结构和生活方式的改变，AS发病率呈逐年上升的趋势，严重地影响着人类的身体健康，成为威胁人类健康和生命的主要杀手。研究人员很早就对AS的发病机制进行了大量的研究，提出了许多理论——从最早的“脂质理论”(Lipid Theory)到后来的“内皮损伤-反应”学说(Responses to Injury)，并试图用这些理论来解释AS的发病机制和指导临床治疗。 随着对AS发病机制研究的逐步深入，人们逐渐认识到AS实际上是一种大血管壁局部和全身系统的炎症状态，慢性炎症过程伴随整个AS发生和发展的过程，从而提出了 AS发病的“炎症假说”。运动对AS的防治有非常积极的作用，以往关于其机制的研究多集中在运动对脂代谢以及血管的舒缩功能的影响上。近年来大量的研究报道，适当的运动能显著改善机体抗炎症的能力，这应该是运动能够有效防治AS的新机制，但有关的实证性研究尚未见报道。本研究以apoE基因缺陷小鼠建立动脉硬化模型，观察有氧运动对动脉硬化斑块形成的影响，重点关注血清、主动脉壁、脂肪组织、骨骼肌相关细胞因子的变化情况，从运动抗炎症的角度来探讨其对AS的影响的细胞分子机制，为运动抗AS的新机制提供实验依据。 实验一：有氧运动对apoE基因缺陷小鼠主动脉脂质斑块面积及血脂水平的影响 本实验以ApoE基因缺陷小鼠建立动脉粥样硬化模型，研究有氧运动对动脉硬化脂质斑块面积和血脂水平的影响。方法：apoE基因缺陷小鼠随机分为安静对照组和运动组(游泳运动，90分钟/次，6次/周，周末休息，共持续10周)，测定和比较两组血脂水平和主动脉血管脂质斑块面积。 结果表明，与对照组相比，10周有氧运动组小鼠主动脉的脂质斑块面积明显缩小(1248.9士204.51μm² vs 1625.7士377.25μm²)，血脂状况显著改善(TC: 614.4±108.3 vs 787.5±127.1 ㎎/dl；TG:53.7±12.9 vs 97. 3±15.4 ㎎/dl；LDL-C: 357.0±66.9 vs 425.1±87.7 ㎎/dl；HDL-C:128.8±13.5 vs 120.9±17.6 ㎎/dl)。实验结果提示，有氧运动能显著抑制动脉粥样硬化的发展，并改善动脉粥样硬化小鼠的血脂水平。 实验二：有氧运动对apoE基因缺陷小鼠血清相关细胞因子水平的影响 本实验以apoE基因缺陷小鼠建立动脉粥样硬化模型，通过检测血清细胞因子TNF-α、IL-6、adiponectin的变化，来观察有氧运动对apoE基因缺陷小鼠系统炎症水平的影响。 动物分组和运动模型同实验一。运用酶联免疫方法(ELISA)检测血清中有关细胞因子的水平。结果显示：10周有氧运动可以显著下调TNF-α(6.03±0. 91 vs 10.37±0.80 pg/ml)和IL-6 (24.39±6.37 vs 181.35±53.12 pg/ml)水平，同时上调adiponectin (123.39±15.95 vs 56.46±8.32 pg/ml)的水平。结果提示，有氧运动可以显著提高apoE基因缺陷小鼠血清中抗炎因子的水平，同时显著降低促炎因子的水平，两者综合作用的结果，可有效改善apoE基因缺陷小鼠系统的炎症状态。 实验三：有氧运动对apoE基因缺陷小鼠主动脉壁炎性因子水平以及巨噬细胞浸润的影响 本实验以VCAM-1、MCP-1的水平以及巨噬细胞(CD68)的浸润为代表性指标，探讨有氧运动对apoE基因缺陷小鼠主动脉壁局部炎症的影响。 动物分组和运动模型同实验一。运用免疫组化的方法对血管壁的炎性因子以及巨噬细胞进行定性、定位和定量分析。结果表明，10周有氧运动可显著下调主动脉壁VCAM-1和MCP-1的表达，同时减轻巨噬细胞在主动脉壁的附着和浸润。提示有氧运动可显著改善动脉硬化局部血管内壁的炎症状态。 实验四：有氧运动对apoE基因缺陷小鼠内脏脂肪“脂肪因子”水平的影响本实验以adiponectin和TNF-α的水平为代表性指标，探讨有氧运动对apoE基因缺陷小鼠内脏脂肪组织炎症状况的影响。 动物分组和运动模型同实验一。运用酶联免疫方法(ELISA)检测内脏脂肪组织adiponectin和TNF-α的水平。结果表明，10周有氧运动可显著下调apoE基因缺陷小鼠内脏脂肪TNF-α的水平(1839.0±289.9 vs 2440.0±632.2 pg/ml)，同时显著上调 adiponectin 的水平(7049.8±650.6 vs 4600.3±475.0 ng/ml)。提示有氧运动可显著改善动脉硬化小鼠内脏脂肪组织的炎症状况。 实验五：有氧运动对apoE基因缺陷小鼠骨骼肌IL-6水平的影响 本实验通过对apoE基因缺陷小鼠骨骼肌IL-6水平的变化的观察，来探讨骨骼肌在运动抗炎症作用中扮演的角色。动物分组和运动模型同实验一。运用酶联免疫方法(ELISA)检测骨骼肌IL-6 的水平。结果表明，10周有氧运动可显著上调apoE基因缺陷小鼠骨骼肌IL-6的水平(963.00 ± 237.63 vs 301.18 ± 96.05 pg/ml)。对于有氧运动对动脉硬化小鼠骨骼肌IL-6的这种上调作用，其确切机理尚需进一步探索。 关键词：有氧运动；动脉粥样硬化；低水平慢性炎症；“运动因子”；脂肪因子

 Atherosclerosis(AS) is a pathological change of aorta. Along with the improvement of the living level and the alteration of lifestyle, the morbidity of AS is increasing year by year. AS has become the main problem of people's health. Many works have been made to explore the mechanism of AS, and many theories have been put forward——from "Lipid Theory" to "Responses to Injury"——to explain the mechanism and instruct the clinical practice. As the research of the mechanism of AS gradually advanced, it is believed that AS is a inflammatory disease of many tissues, especially aorta and adipose tissue, and the systemic chronic inflammation is present to the whole progress of AS. Physical activity is beneficial to AS, and it has been believed that the effects of exercise to the metabolism of fat is the main mechanism. Recently, more and more researches show the positive effect of regular exercise to the anti-inflammatory ability of organism. This should be a new mechanism of anti-atherosclerotic ability of exercise. Few has been done about the anti-inflammatory effects of regular exercise on AS. In this study, apoE-deficient mouse was selected as AS model so as to observe the anti-inflammatory effects of aerobic exercise on AS, through the change of inflammatory cytokines in serum, aorta wall, adipose tissue and skeletal muscle . EXPERIMENT 1:The Effect of Aerobic Exercise on Atheromatous Plaques Area and serum lipid of ApoE-deficient Mouse ApoE-deficient mouse was used as AS model to approach the effect and mechanism of aerobic exercise on formation of atherosclerotic lesions. METHODS: 16 ApoE-deficient mice were randomly divided into control group (CG) and exercise group (EG swimming, 90min/d, 6d/w, 10 wks), the lesion area and serum lipid were tested. RESULTS: Compared with CG the lesion area in the aorta of EG was significantly less than that of the CG (1248.9 士 204.51μm² vs 1625.7 士 377.25 μm²). And the serum lipid was improved significantly (TC: 614·4±108.3 vs 787·5±127.1 ㎎/dl; TG: 53.7±12.9 vs 97.3±15.4 ㎎/dl; LDL-C: 357.0±66.9 vs 425.1±87.7 ㎎/dl; HDL-C: 128.8±13.5 vs 120.9±17.6 ㎎/dl). The results suggested that aerobic exercise significantly decreased the development of atherosclerotic plaque in apoE-deficient mice and simultaneously improved the fat metabolism. EXPERIMENT 2: The Effect of Aerobic Exercise on Serum Cytokines Animal model same as Experiment 1. The concentrations of TNF-α, IL-6 and adiponectin were tested to explore the effect of aerobic exercise on the systemic inflammatory level of apoE-deficient mouse. METHODS'. The exercise model was the same as EXPERIMENT 1. ELISA was used to test the serum cytokines. RESULTS：Covcvpared with CG, the serum levels of TNF-α and IL-6 were significantly down-regulated in the EG (TNF-α: 6.03±0.91 vs 10.37±0.80 pg/ml; IL-6: 24.39±6. 37 vs 181.35±53.12pg/ml) , and the adiponectin level was up-regulated significantly (123.39±15.95 vs 56.46±8.32μg/ml). This result showed that aerobic exercise significantly decreased the pro-inflammatory cytokine and increased the anti-inflammatory cytokine simultaneously in apoE-deficient mice . The systemic inflammation can be effectively . improved from aerobic exercise. EXPERIMENT 3: The Effect of Aerobic Exercise on Pro-inflammatory Factors and Macrophages at ApoE-deficient Mouse Aorta Animal model same as Experiment 1. The expression of VCAM-1, MCP-1 and the accumulation of macrophages (CD68) in aorta were determined to explore the effect of aerobic exercise on the local inflammatory level of aorta. METHODS:. The exercise model was the same as EXPERIMENT 1. The expression of VCAM-1, MCP-1 and the accumulation of macrophages (CD68) in aorta were determined by immunohistochemical method. RESULTS: Compared with CG, the expression of VCAM-1, MCP-1 and the accumulation of macrophages (CD68) in aorta were all down-regulated. This result suggested that aerobic exercise improved the local inflammation in aorta. EXPERIMENT 4: The Effect of Aerobic Exercise on Adipokines of Visceral Adipose Tissue Animal model same as Experiment 1. The TNF-α and Adiponectin levels of visceral adipose tissue were tested to explore the effect of aerobic exercise on the adipose tissue inflammation. METHODS: The exercise model was the same as EXPERIMENT 1. The TNF-α and Adiponectin levels of visceral adipose tissue were tested by ELISA. RESULTS:Compared with CG, the level of TNF-α in visceral adipose tissue was significantly down-regulated in EG (1839.0±289.9 vs 2440. 0±632. 2pg/ml), and the adiponectin level was up-regulated significantly (7049. 8±650.6 vs 4600.3±475. 0ng/ml). This result suggested that aerobic exercise significantly improved the local inflammation in visceral adipose tissue . EXPERIMENT 5: The Effect of Aerobic Exercise on IL-6 Level of Skeletal Muscle Animal model same as Experiment 1. The IL-6 level of skeletal muscle was tested to explore the possible function of skeletal muscle in the anti-inflammation effect of aerobic exercise. METHODS: The exercise model was the same as EXPERIMENT 1. The IL-6 level of skeletal muscle was tested by ELISA. RESULTS: Compared with CG the level of IL-6 of skeletal muscle was significantly increased in EG (963.00±237.63 vs 301.18±96.05pg/ml). To explain the exact means of this result, further research is required. Key Words: aerobic exercise; atherosclerosis; low-grade chronic inflammation "exercise factor"; adipokine