有氧运动对高同型半胱氨酸血症载脂蛋白E基因敲除小鼠动脉粥样硬化的影响

Role of Aerobic Exercise on Atherosclerosis Accelerated by Hyperhomocysteinemia in Apolipoprotein E^(-/-) Mice

目的观察有氧运动训练对高同型半胱氨酸血症(HHcy)小鼠血浆同型半胱氨酸水平(Hcy)的影响,探讨有氧运动是否能够延缓HHcy致动脉粥样硬化。方法 6周龄雌性载脂蛋白E基因敲除(ApoE-/-)小鼠随机分为三组:对照组、HHcy组和HHcy+有氧运动组。饮用水中加入Hcy制作HHcy模型。HHcy+有氧运动组在1周适应性训练后进行8周跑台训练(0°,15 m/min,60 min/d,每周训练5天)。采用酶法检测血浆Hcy和血脂水平。主动脉根部切片,油红O染色,计算动脉粥样硬化斑块面积。结果 HHcy组血浆Hcy水平与对照组相比明显增高(20.88±5.79μmol/L比7.80±1.10μmol/L,P=0.001),HHcy+有氧运动组血浆Hcy水平较HHcy组明显下降(14.01±2.30μmol/L比20.88±5.79μmol/L,P=0.016)。三组之间体重增长、饮水量及血浆总胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、甘油三酯水平无显著性差异。与对照组相比,HHcy组动脉粥样硬化斑块面积[(9.24±9.02)×10-4 mm2比(15.55±4.64)×10-4 mm2,P=0.034]及斑块负荷(12.20%±12.09%比19.86%±6.30%,P=0.047)明显增加,HHcy+有氧运动组较HHcy组斑块面积[(15.55±4.64)×10-4mm2比(8.62±7.55)×10-4mm2,P=0.024]及斑块负荷(19.86%±6.30%比10.62%±9.06%,P=0.021)明显降低。结论有氧运动可以降低HHcyApoE-/-小鼠血浆Hcy水平,延缓动脉粥样硬化进展,该作用独立于血脂水平的改变。

Aim To investigate whether aerobic exercise could decrease plasma homocysteine （Hcy） level and reduce atherosclerosis accelerated by hyperhomocysteinemia （HHcy） in ApoE-/- mice. Methods Six-week-old fe- male ApoE -/- mice were assigned to three groups： control group, HHcy group and HHcy ＋ exercise group. HHcy animal model was made by feeding a high Hcy chow. After 1 week of acclimatization, HHcy ＋ exercise group was trained in a motorized rodent treadmill for 8 weeks （slope： 0°, speed： 15 m/min, 60 min/d, 5 d/wk）. Plasma Hcy level and lipid levels were determined enzymatically by auto-biochemistry analysis system. Aortic roots were isolated for immunohisto- chemistry to compare the plaques＇ areas. Results Plasma Hcy levels in HHcy group were higher than control group, furthermore, the Hcy levels significantly decreased in HHcy ＋ exercise group compared with HHcy group. There were not significant differences in body weight, daily drinking amount, plasma total cholesterol, LDLC, HDLC and triglyceride con- centrations in the three groups. Compared with control group, atherosclerotic plaque area and plaque burden were in- creased in HHcy group. However, the plaque area and plaque burden in HHcy ＋ exercise group were decreased when compared with HHcy group. Conclusion Aerobic exercise decreases plasma Hcy levels and reduces the development of atherosclerosis in HHey ApoE-/- mice, which does not depend on the decrease of cholesterol levels.