有氧运动改善心肌梗死心脏交感神经重构的抗炎机制

The anti- inflammatory mechanism of aerobic exercise ameliorating sympathetic neural remodeling after myocardial infarction

目的:探讨有氧运动是否通过抑制NF-κB通路激活改善心肌梗死后交感神经重构。方法:45只健康雄性SD大鼠随机分为假手术组、心肌梗死组、心肌梗死+有氧运动组。结扎冠状动脉左前降支制备大鼠心肌梗死的模型,术后1周心肌梗死+有氧运动组成活大鼠进行4周跑台运动。采用免疫组织化学方法观察心肌梗死灶周及左室游离壁TH阳性神经纤维分布及表达;采用western blot检测心肌中NF-κB p65及IκBα蛋白表达;采用实时定量RTPCR检测IL-1β及TNF-αmRNA表达。结果:与假手术组大鼠相比,心肌梗死组心肌中TH阳性神经纤维密度明显增加,形态粗大且空间分布紊乱,尤以梗死灶周为著;有氧运动干预后TH阳性神经纤维密度显著降低,形态更趋于正常。心肌梗死可激活NF-κB通路,表现为心肌核蛋白中NF-κB p65含量增加,胞质蛋白中IκBα含量降低,其下游转录产物IL-1β及TNF-αmRNA明显上调;而有氧运动干预可明显抑制NF-κB通路激活,减少NF-κB p65及增加IκBα蛋白表达,并下调IL-1β及TNF-αmRNA表达。结论:有氧运动通过抑制心肌梗死后NF-κB及其转录系统的激活,减少心肌组织炎症反应的过度放大,抑制交感神经过度再生,从而改善心肌梗死后交感神经重构。

Objective： To investigate whether aerobic exercise ameliorates sympathetic neural remodeling via inhibiting nuclear factor- κB（ NF- κB） activity after myocardial infarction（ MI）. Methods： 45 male Sprague- Dawley rats were randomly divided into 3 groups： sham group,MI group and MI with aerobic exercise（ MI ＋ ME） group. An MI model was induced by ligation of the coronary artery; the rats in MI ＋ ME group were assigned to 4 weeks of exercise. Immunohistochemistry was used to measure the density of nerve fibers positive for tyrosine hydroxylase（ TH）. The protein levels of NF- κB p65 and inhibitor κBα（ IκBα） were detected by western blot analysis. The mRNA levels of interleukin- 1β（ IL- 1β） and tumor necrosis factor- α（ TNF- α） were examined by quantitative real- time PCR. Results： Compared with the sham- operated hearts,MI increased the density of TH- positive fibers,and the distribution and structure of regenerated nerves were heterogeneous in MI hearts,especially in the infarcted border. Moreover,the TH- positive nerve fiber density was lower with MI ＋ ME than MI alone. MI upregulated the protein levels of NF- κB p65 and downregulated IκBα. Aerobic exercise significantly reduced the MI- induced nuclear expression of NF- κB p65 and increased the MI- induced cytoplasmic expression of IκBα. In line with the NF- κB activation,mRNA levels of IL- 1β and TNF- α were higher in MI than sham- operated hearts,however,when NF- κB activation was inhibited by aerobic exercise,MI- induced transcription of these genes was suppressed. Conclusions： Aerobic exercise ameliorates sympathetic nerve sprouting in rats after MI is associated in part with inhibiting NF- κB activity.