耐力训练对动脉粥样硬化ApoE^-/-小鼠主动脉NF-κB和MMP-9表达的影响

Effect of Endurance Exercise on the Expression of NF-κB and MMP-9 in Aorta of Atherosclerotic ApoE^(-/-) Mice

目的:探讨耐力训练对动脉粥样硬化(AS)载脂蛋白E基因敲除(ApoE-/-)小鼠主动脉核因子-κB(NF-κB)和基质金属蛋白酶-9(MMP-9)表达的影响及其在抗AS中的作用。方法:36只8周龄ApoE-/-小鼠随机分为14周AS模型组(H组)、26周AS模型组(HH组)、14周造模+12周运动干预组(HE组),每组12只,均饲以高脂膳食饲料。HE组小鼠经14周高脂饲养形成AS后,开始在活动跑台上进行12周耐力训练(13 m/min,60min/次,每周5次)。另选取12只8周龄C57BL/6J小鼠作为对照组(N组),饲以标准饲料。制备主动脉根部冰冻切片,行HE染色观察主动脉病理变化,行原位杂交法测定主动脉NF-κB mRNA表达,行免疫组化法测定主动脉NF-κBp65及MMP-9蛋白表达,其表达量用阳性细胞%表示。结果:①14周高脂膳食后H组小鼠发生AS;HH组较H组病变加重,而HE组较HH组病变减轻。②HH组小鼠主动脉NF-κB mRNA及NF-κBp65阳性细胞%均显著高于N组,而HE组显著低于HH组(P<0.01)。③HH组小鼠主动脉MMP-9阳性细胞%显著高于N组,而HE组显著低于HH组(P<0.01)。结论:耐力训练降低AS小鼠主动脉NF-κB表达和MMP-9表达,发挥抗AS作用,可能是运动防治AS的机制之一。

Objective The study was to investigate the effects of endurance exercise on the expression of NF-κB and MMP-9,and the protection against atherosclerosis in apolipoprotein E-knockout（ApoE-/-）mice.Methods Eight-week-old ApoE-/-mice（n=36）were randomly and equally divided into fourteen-week model group（H）,twenty-six-week high fat diet group（HH）,fourteen-week high fat diet and twelve-week exercise group（HE）.All groups were fed with high fat diet.After 14 weeks,group HE underwent endurance exercise on a treadmill for 12 weeks（13 m/min,60 minutes per day,5 days per week）.Eight-week-old C57BL/6J mice（fed with normal forage for 26 weeks）were used as their controls（N,n=12）.Frozen section of aortic root（HE stain）and the expression of NF-κB were prepared and measured,the percentage of NF-Bp65 and MMP-9 positive cells was mea-sured by immunohistochemistry in vivo.Results ① Fourteen-week high fat diet resulted in development of atherosclerosis in rats.The severity of atherosclerosis was more evident in group HH,however,the severity of atherosclerosis in group HE was signif icantly lighter than that in group HE.② As compared with group N,the NF-κB mRNA and the percentage of NF-Bp65 positive cells increased signif icantly in group HH,while the levels in group HE were signif icantly lower than that in group HH（P〈0.01）.③ As compared with group N,the percentage of MMP-9 positive cells increased signif icantly in group HH,while the level in group HE was signif icantly lower than that in group HH（P〈0.01）.Conclu-sion Endurance exercise decreased the expression of NF-κB and MMP-9 in aorta of mice,demonstrat-ing that it could protect apolipoprotein E-knockout mice against the development of atherosclerosis.