交感神经阻滞通过激活 JAK2-STAT3 介导的信号级联反应促进大鼠心肌炎模型中的抗炎反应：具有临床意义的新机制。
Sympathetic nerve blocks promote anti-inflammatory response by activating the JAK2-STAT3-mediated signaling cascade in rat myocarditis models: A novel mechanism with clinical implications.
机构信息
Division of Cardiology, Yonsei University College of Medicine, Seoul, South Korea; Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, South Korea.
Division of Cardiology, Yonsei University College of Medicine, Seoul, South Korea.
出版信息
Heart Rhythm. 2018 May;15(5):770-779. doi: 10.1016/j.hrthm.2017.09.039. Epub 2017 Sep 28.
BACKGROUND
Left stellectomy has become an important therapeutic option for patients with potentially fatal arrhythmias. However, the antiarrhythmic mechanism of left stellectomy is not well known. The cholinergic anti-inflammatory pathway (CAIP) is a complex immune mechanism that regulates peripheral inflammatory responses.
OBJECTIVE
The purpose of this study was to evaluate the effect of left stellectomy on CAIP using rat experimental autoimmune myocarditis (EAM) models.
METHODS
EAM was produced by injecting 2 mg of porcine cardiac myosin into the footpads of rats. Left stellectomy was performed before EAM induction. We evaluated the effect of left stellectomy on arrhythmic events, survival, inflammation, and CAIP in rats without and with EAM.
RESULTS
Left stellectomy prevented arrhythmia and improved survival in EAM rats. Left stellectomy decreased the levels of tumor necrosis factor α, interleukin 6, and high mobility group box 1 (P < .05 vs EAM) in serum and heart tissues from EAM rats. In heart rate variability analysis, high-frequency peaks of the power spectrum densities, reflecting parasympathetic cardiovagal tone, were significantly decreased in EAM rats, but increased after left stellectomy. The ratios of phosphorylated STAT3/STAT3 (signal transducer and activator of transcription 3) and phosphorylated JAK2/JAK2 (Janus kinase 2) decreased in cell lysates of the spleen, liver, and heart in EAM rats. However, the same ratios significantly increased after left stellectomy. Nuclear factor κB in cell lysates of the spleen, liver, and heart increased in EAM rats, but decreased after left stellectomy.
CONCLUSION
In EAM models, left stellectomy increased survival of the rats while showing antiarrhythmic effects with reduced inflammation via activation of the JAK2-STAT3-mediated signaling cascade. Our findings suggest an exciting opportunity to develop new and novel therapeutics to attenuate cardiac inflammation.
背景
左侧星状神经节切除术已成为治疗潜在致命性心律失常患者的重要治疗选择。然而，左侧星状神经节切除术的抗心律失常机制尚不清楚。胆碱能抗炎通路（CAIP）是一种调节外周炎症反应的复杂免疫机制。
目的
本研究旨在使用大鼠实验性自身免疫性心肌炎（EAM）模型评估左侧星状神经节切除术对 CAIP 的影响。
方法
通过向大鼠足底注射 2mg 猪心肌肌球蛋白来诱导 EAM。在 EAM 诱导前进行左侧星状神经节切除术。我们评估了左侧星状神经节切除术对无 EAM 和有 EAM 的大鼠心律失常事件、生存、炎症和 CAIP 的影响。
结果
左侧星状神经节切除术可预防 EAM 大鼠的心律失常并提高其生存率。左侧星状神经节切除术降低了 EAM 大鼠血清和心脏组织中肿瘤坏死因子-α、白细胞介素 6 和高迁移率族蛋白 1（P<.05 比 EAM）的水平。在心率变异性分析中，EAM 大鼠的功率谱密度高频峰值，反映副交感神经心迷走神经张力，显著降低，但左侧星状神经节切除术后增加。EAM 大鼠脾、肝和心脏细胞裂解物中磷酸化 STAT3/STAT3（信号转导和转录激活因子 3）和磷酸化 JAK2/JAK2（Janus 激酶 2）的比值降低，但左侧星状神经节切除术后增加。脾、肝和心脏细胞裂解物中的核因子κB 在 EAM 大鼠中增加，但左侧星状神经节切除术后减少。
结论
在 EAM 模型中，左侧星状神经节切除术增加了大鼠的生存率，同时通过激活 JAK2-STAT3 介导的信号级联反应，显示出抗心律失常作用，减轻了炎症。我们的研究结果表明，有机会开发新的治疗方法来减轻心脏炎症。
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