Wang Youhua, Tian Zhenjun, Zang Weijin, Jiang Hongke, Li Youyou, Wang Shengpeng, Chen Shengfeng
Department of Physical Education, Shaanxi Normal University, Xi'an, Shaanxi, China, Department of Physiology, University of Maryland School of Medicine, Baltimore, MD, USA.
Department of Physical Education, Shaanxi Normal University, Xi'an, Shaanxi, China.
Physiol Rep. 2015 Apr;3(4). doi: 10.14814/phy2.12339.
Myocardial infarction (MI) induces cardiac dysfunction and insulin resistance (IR). This study examines the effects of MI-related IR on vasorelaxation and its underlying mechanisms, with a specific focus on the role of exercise in reversing the impaired vasorelaxation. Adult male Sprague-Dawley rats were divided into three groups: Sham, MI, and MI+Exercise. MI+Exercise rats were subjected to 8 weeks of treadmill training. Cardiac contraction, myocardial and arterial structure, vasorelaxation, levels of inflammatory cytokines, expression of eNOS and TNF-α, and activation of PI3K/Akt/eNOS and p38 mitogen-activated protein kinase (p38 MAPK) were determined in aortas. MI significantly impaired endothelial structure and vasodilation (P < 0.05-0.01), as indicated by decreased arterial vasorelaxation to ACh and insulin. MI also attenuated the myocardial contractile response, decreased aortic PI3K/Akt/eNOS expression and phosphorylation by insulin, and increased IL-1β, IL-6, and TNF-α expression and p38 MAPK activity (P < 0.05-0.01). Exercise improved insulin sensitivity in aortas, facilitated myocardial contractile response and arterial vasorelaxation to ACh and insulin, and increased arterial PI3K/Akt/eNOS activity. Moreover, exercise markedly reversed increased p38 MAPK activity and normalized inflammatory cytokines in post-MI arteries. Inhibition of PI3K with LY-294002, and eNOS with L-NAME significantly blocked arterial vasorelaxation and PI3K/Akt/eNOS phosphorylation in response to insulin. In conclusion, these results demonstrate that endothelial dysfunction in response to insulin plays an important role in MI-related IR. The reversal of IR by exercise is most likely associated with normalizing inflammatory cytokines, increasing the activation of PI3K/Akt/eNOS, and reducing the activation of p38 MAPK.
心肌梗死（MI）会引发心脏功能障碍和胰岛素抵抗（IR）。本研究探讨了MI相关的IR对血管舒张的影响及其潜在机制，特别关注运动在逆转受损血管舒张方面的作用。成年雄性Sprague-Dawley大鼠分为三组：假手术组、MI组和MI+运动组。MI+运动组大鼠接受8周的跑步机训练。测定主动脉的心脏收缩功能、心肌和动脉结构、血管舒张功能、炎性细胞因子水平、eNOS和TNF-α的表达以及PI3K/Akt/eNOS和p38丝裂原活化蛋白激酶（p38 MAPK）的激活情况。MI显著损害内皮结构和血管舒张功能（P<0.05-0.01），表现为动脉对乙酰胆碱（ACh）和胰岛素的血管舒张反应降低。MI还减弱了心肌收缩反应，降低了胰岛素对主动脉PI3K/Akt/eNOS的表达和磷酸化作用，并增加了IL-1β、IL-6和TNF-α的表达以及p38 MAPK活性（P<0.05-0.01）。运动改善了主动脉的胰岛素敏感性，促进了心肌收缩反应以及动脉对ACh和胰岛素的血管舒张反应，并增加了动脉PI3K/Akt/eNOS活性。此外，运动显著逆转了MI后动脉中p38 MAPK活性的增加，并使炎性细胞因子恢复正常。用LY-294002抑制PI3K以及用L-NAME抑制eNOS可显著阻断胰岛素诱导的动脉血管舒张和PI3K/Akt/eNOS磷酸化。总之，这些结果表明，胰岛素引起的内皮功能障碍在MI相关的IR中起重要作用。运动逆转IR很可能与炎性细胞因子恢复正常、增加PI3K/Akt/eNOS的激活以及降低p38 MAPK的激活有关。
