Department of Rehabilitation, Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu 210009, P.R. China.
Department and Institute of Cardiology, Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu 210009, P.R. China.
Int J Mol Med. 2018 Nov;42(5):2867-2880. doi: 10.3892/ijmm.2018.3841. Epub 2018 Aug 24.
Exercise induces a number of benefits, including angiogenesis in post‑myocardial infarction (MI); however, the underlying mechanisms have not been fully clarified. Neurotrophic brain‑derived neurotrophic factor (BDNF) serves a protective role in certain adult cardiac diseases through its specific receptor, BDNF/NT‑3 growth factors receptor (TrkB). The present study explored the mechanisms by which exercise improves cardiac function, with a focus on the involvement of the BDNF/TrkB axis. MI rats were assigned to Sham, sedentary, exercise, exercise with K252a (a TrkB inhibitor), and exercise with NG‑nitro‑L‑arginine methyl ester (L‑NAME) groups. The exercise group was subjected to 8 weeks of treadmill running. The results demonstrated that the rats in the exercise group exhibited increased myocardial angiogenesis and improved cardiac function, which was attenuated by K252a. Exercise induced activation of the BDNF/TrkB axis in the ischaemic myocardium and increased serum BDNF levels were abated by exposure to L‑NAME. Improvements in angiogenesis and left ventricular function exhibited a positive association, with changes in serum BDNF. In the in vitro experiments, human umbilical vein endothelial cells were exposed to shear stress (SS) of 12 dyn/cm2 to mimic the effects of exercise training on vascular tissue. An increased tube‑forming capacity, and a nitric oxide (NO)‑dependent prolonged activation of the BDNF/TrkB‑full‑length axis over 12 h, but not the TrkB‑truncated axis, was observed. The SS‑related angiogenic response was attenuated by TrkB inhibition. Overall, these results demonstrate that exercise confers certain aspects of its cardioprotective effects through the activation of the BDNF/TrkB axis in an NO‑dependent manner, a process in which fluid‑induced SS may serve a crucial role.
运动可带来多种益处，包括心肌梗死后的血管生成；然而，其潜在机制尚未完全阐明。神经营养因子脑源性神经营养因子（BDNF）通过其特定受体 BDNF/NT-3 生长因子受体（TrkB）在某些成人心脏疾病中发挥保护作用。本研究探讨了运动改善心脏功能的机制，重点关注 BDNF/TrkB 轴的参与。将 MI 大鼠分为假手术、久坐不动、运动、运动加 K252a（TrkB 抑制剂）和运动加 NG-硝基-L-精氨酸甲酯（L-NAME）组。运动组进行 8 周的跑步机跑步。结果表明，运动组大鼠心肌血管生成增加，心功能改善，而 K252a 则减弱了这种作用。运动诱导缺血心肌中 BDNF/TrkB 轴的激活，并增加了血清 BDNF 水平，而 L-NAME 则削弱了这一作用。血管生成和左心室功能的改善与血清 BDNF 的变化呈正相关。在体外实验中，将人脐静脉内皮细胞暴露于 12dyn/cm2 的切应力（SS）下，模拟运动训练对血管组织的影响。结果发现，与对照组相比，血管形成能力增强，BDNF/TrkB 全长轴的 NO 依赖性激活时间延长至 12 小时，而 TrkB 截断轴的激活时间则没有延长。TrkB 抑制减弱了 SS 相关的血管生成反应。总之，这些结果表明，运动通过 NO 依赖性方式激活 BDNF/TrkB 轴，从而发挥其部分心脏保护作用，在这个过程中，液流诱导的 SS 可能发挥关键作用。
