有氧运动对载脂蛋白E基因缺陷小鼠颈动脉粥样硬化斑块易损性的影响  

The effects of aerobic exercise on atherosclerotic plaques in apolipoprotein E gene deficient mice

作　　者：张栩[1,2] 邵世修[4] 李铁山[3] 张勇[2] 毕建忠[1] 

机构地区：[1]山东大学第二医院神经内科,济南250033 [2]青岛大学医学院附属医院神经内科 [3]青岛大学医学院附属医院康复医学科 [4]青岛大学医学院附属医院泌尿外科

出　　处：《中华物理医学与康复杂志》2011年第8期561-565,共5页Chinese Journal of Physical Medicine and Rehabilitation

摘　　要：目的探讨有氧运动对载脂蛋白E（ApoE）基因缺陷小鼠颈动脉粥样硬化斑块易损性及斑块内基质金属蛋白酶-9（MMP-9）、基质金属蛋白酶-14（MMP-14）水平变化的影响。方法将80只雄性载脂蛋白E基因缺陷小鼠随机分为有氧运动组（n=40）及对照组（n=40），2组小鼠均通过颈动脉套管术构建颈动脉粥样硬化动物模型。造模成功4周后，有氧运动组开始进行电动跑台有氧运动训练，每日1次，每次1h，持续训练8周，对照组限制活动8周。造模成功12周后，测量2组小鼠的血脂水平，评价颈动脉粥样硬化斑块形态结构，测量斑块面积和纤维帽厚度，对颈动脉斑块进行脂质含量、胶原含量检测，计算斑块易损指数。并通过免疫组织化学方法检测斑块内MMP-9、MMP-14水平。逆转录一多聚酶链反应（RT—PCR）检测MMP-9、MMP-14mRNA的表达量。免疫印记Westernblot检测斑块内MMP-9、MMP-14蛋白表达。结果经血液学检测，2组间血脂水平差异无统计学意义（P〈0．05）；经病理学检测2组间的斑块面积差异无统计学意义（P〈0．05），而有氧运动组纤维帽厚度、帽／核比值、胶原含量均明显增加，与对照组比较，差异有统计学意义（P〈0．05）。另，2组间的斑块破裂率和斑块易损指数差异亦有统计学意义（P〈0．05）。有氧运动组斑块内MMP-9和MMP-14的表达量均显著低于对照组（P〈0．05）；有氧运动组斑块内MMP-9mRNA和MMP-14mRNA的表达量亦显著低于对照组，差异有统计学意义（P〈0．05）；有氧运动组颈动脉斑块组织中MMP-9蛋白和MMP-14蛋白的表达量显著低于对照组，差异有统计学意义（P〈0．05）。结论有氧运动降低ApoE基因缺陷小鼠颈动脉粥样硬化斑块内MMP-9，MMP-14表达，通过增强斑块稳定性，减弱易损性，起到抗动脉粥样硬化作用。[ Abstract] Objective To investigate the influence of aerobic exercise on the vulnerability of atherosclerotic plaques and to observe the concentration of matrix metalloproteinase-9 （MMP-9） and matrix metalloproteinase-14 （MMP-14） in carotid atherosclerotic plaques in apolipoprotein E （ApoE） gene deficient mice. Methods Eighty male, ApoE gene deficient mice were divided into two equal groups： an aerobic exercise group and a limited action control group. Carotid atherosclerotic lesions were induced by perivascular constrictive collars placed on the right common carotid artery. Blood lipid levels in the exercise group were measured after 8 weeks of treadmill running and also in the control group. The morphological characteristics of carotid atherosclerotic plaques were observed in the two groups. Plaque area and fibrous cap thickness were measured. Lipid and collagen positive areas were quantified and the ratios correlated with the entimal areas were calculated. Plaque rupture rate and vulnerable index were calculated. Immunostaining was used to detect MMP＇-9 and MMP-14 expression in the atherosclerotic plaques. The mRNA levels of MMP-9 and MMP-14 mRNA in the fresh carotid plaques were quantified using a real-time reverse-transcriptase pol- ymerase chain reaction （RT-PCR）. Western blotting was performed for examining MMP-9 and MMP-14 protein ex- pression in the fresh carotid plaques. Results No significant difference in serum lipid profiles or plaque area was found between the exercise and control groups. Compared with the control group, mean fibrous cap thickness, cap/ core ratio and collagen content were all significantly higher in the exercise group, and lipid content was significantly lower. Plaque rupture rate and the vulnerable index were both significantly lower in the exercise group. Immunostaining showed that MMP-9 and MMP-14 expression were lower in the exercise group compared with the control group. The mRNA expression of MMP-9 and MMP-14 was also significantly lower. Conclusions Aero

关 键 词：动脉粥样硬化 有氧运动 载脂蛋白E基因缺陷 MMP-9 MMP-14 

分 类 号：R743[医药卫生—神经病学与精神病学]