Chung Chee Hooi, Bretherton Beatrice, Zainalabidin Satirah, Deuchars Susan A, Deuchars Jim, Mahadi Mohd Kaisan
Drug and Herbal Research Centre, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom.
Front Neurosci. 2020 Sep 8;14:906. doi: 10.3389/fnins.2020.00906. eCollection 2020.
Myocardial infarction (MI) reperfusion therapy causes paradoxical cardiac complications. Following restoration of blood flow to infarcted regions, a multitude of inflammatory cells are recruited to the site of injury for tissue repair. Continual progression of cardiac inflammatory responses does, however, lead to adverse cardiac remodeling, inevitably causing heart failure.
Increasing evidence of the cardioprotective effects of both invasive and non-invasive vagal nerve stimulation (VNS) suggests that these may be feasible methods to treat myocardial ischemia/reperfusion injury anti-inflammatory regulation. The mechanisms through which auricular VNS controls inflammation are yet to be explored. In this review, we discuss the potential of autonomic nervous system modulation, particularly the parasympathetic branch, in ameliorating MI. Novel insights are provided about the activation of the cholinergic anti-inflammatory pathway on cardiac macrophages. Acetylcholine binding to the α7 nicotinic acetylcholine receptor (α7nAChR) expressed on macrophages polarizes the pro-inflammatory into anti-inflammatory subtypes. Activation of the α7nAChR stimulates the signal transducer and activator of transcription 3 (STAT3) signaling pathway. This inhibits the secretion of pro-inflammatory cytokines, limiting ischemic injury in the myocardium and initiating efficient reparative mechanisms. We highlight recent developments in the controversial auricular vagal neuro-circuitry and how they may relate to activation of the cholinergic anti-inflammatory pathway.
Emerging published data suggest that auricular VNS is an inexpensive healthcare modality, mediating the dynamic balance between pro- and anti-inflammatory responses in cardiac macrophages and ameliorating cardiac ischemia/reperfusion injury.
心肌梗死（MI）再灌注治疗会引发矛盾的心脏并发症。在梗死区域恢复血流后，大量炎症细胞被招募到损伤部位进行组织修复。然而，心脏炎症反应的持续进展确实会导致不良的心脏重塑，不可避免地引发心力衰竭。
越来越多的证据表明，有创和无创迷走神经刺激（VNS）均具有心脏保护作用，这表明这些可能是治疗心肌缺血/再灌注损伤抗炎调节的可行方法。耳穴VNS控制炎症的机制尚待探索。在本综述中，我们讨论了自主神经系统调节，特别是副交感神经分支，在改善心肌梗死方面的潜力。提供了关于心脏巨噬细胞上胆碱能抗炎途径激活的新见解。乙酰胆碱与巨噬细胞上表达的α7烟碱型乙酰胆碱受体（α7nAChR）结合，将促炎亚型极化转变为抗炎亚型。α7nAChR的激活刺激信号转导和转录激活因子3（STAT3）信号通路。这抑制了促炎细胞因子的分泌，限制了心肌的缺血损伤并启动了有效的修复机制。我们强调了有争议的耳穴迷走神经回路的最新进展以及它们与胆碱能抗炎途径激活的可能关系。
新发表的数据表明，耳穴VNS是一种廉价的医疗保健方式，可调节心脏巨噬细胞中促炎和抗炎反应之间的动态平衡，并改善心脏缺血/再灌注损伤。
