[1]史晓宇 江洪 余锂镭.左侧星状神经节慢性白细胞介素6过表达对心脏电生理的影响及机制探讨[J].心血管病学进展,2025,(6):565.[doi:10.16806/j.cnki.issn.1004-3934.2025.06.019]
 SHI Xiaoyu,JIANG Hong,YU Lilei.Effect of Chronic Interleukin 6 Overexpression in the Left Stellate Ganglion on Cardiac Electrophysiology and Investigation of Mechanisms[J].Advances in Cardiovascular Diseases,2025,(6):565.[doi:10.16806/j.cnki.issn.1004-3934.2025.06.019]
点击复制

左侧星状神经节慢性白细胞介素6过表达对心脏电生理的影响及机制探讨()

《心血管病学进展》[ISSN:51-1187/R/CN:1004-3934]

卷:
期数:
2025年6期
页码:
565
栏目:
论著
出版日期:
2025-06-25

文章信息/Info

Title:
Effect of Chronic Interleukin 6 Overexpression in the Left Stellate Ganglion on Cardiac Electrophysiology and Investigation of Mechanisms
作者:
史晓宇 江洪 余锂镭
(武汉大学人民医院心血管内科 武汉大学心血管病研究所 心血管病湖北省重点实验室 武汉大学心脏自主神经研究中心,湖北 武汉 430060)
Author(s):
SHI XiaoyuJIANG HongYU Lilei
(Department of Cardiology,Renmin Hospital of Wuhan University,Cardiovascular Research Institute of Wuhan University,Hubei Key Laboratory of Cardiology,Cardiac Autonomic Nervous System Research Center of Wuhan University,Wuhan 430060,Hubei,China)
关键词:
白细胞介素6左侧星状神经节自主神经系统
Keywords:
Interleukin 6 Left stellate ganglion Autonomic nervous system
DOI:
10.16806/j.cnki.issn.1004-3934.2025.06.019
摘要:
目的 探讨炎症因子白细胞介素6(IL-6)在左侧星状神经节(LSG)中慢性过表达对心脏电生理的影响及机制。 方法 将16只健康比格犬随机分为IL-6组( n=8)和对照组(n=8)两组,IL-6组对LSG进行多点位微量注射AAV-IL-6,对照组显微注射等量生理盐水,注射前收集血清,测量LSG活性。术前和术后第30天进行24小时动态心电图检测,以记录心电生理指标:室性心律失常(VA)发生率、QT间期、QTc、QT间期离散度、QTc离散度),在术后第31天收集血清并再次测量LSG活性,收集LSG组织进行分子检测。结果 基础状态下,两组心脏电生理指标、血清 去甲肾上腺素水平、LSG活性无显著差异。IL-6慢性过表达30 d 后,IL-6组VA发生次数显著增加(P<0.05),其次,QT间期、QTc均显著缩短(P<0.05),QT间期离散度、QTc离散度均显著增加(P<0.05),VA评分显著增加。此外,与对照组相比,IL-6组血清去甲肾上腺素水平及LSG活性显著增加,LSG突触素密度显著增加(P<0.05)。结论 LSG中IL-6慢性过表达降低心电生理稳定性、增加VA发生次数,可能与LSG重构诱导的自主神经功能紊乱有关。
Abstract:
Objective To examine the effects and underlying mechanisms of chronic overexpression of the inflammatory cytokine interleukin 6 (IL-6) in the left stellate ganglion (LSG) on cardiac electrophysiological properties. Methods Sixteen healthy Beagles were randomly assigned to two groups: the IL-6 group (n=8) and the control group (n=8). In the IL-6 group,multisite microinjections of AAV-IL-6 were administered to the LSG,while the control group received an equal volume of saline. Prior to injection,serum samples were collected,and LSG activity was measured. A 24-hour ambulatory electrocardiogram monitoring was performed both preoperatively and on postoperative day 30,including the incidence of ventricular arrhythmias (VA),QT interval,QTc,QT interval dispersion,and QTc dispersion. Serum was again collected,and LSG activity was measured on day 31 post-surgery,with LSG tissues harvested for molecular analysis. Results At baseline,no significant differences were observed between the two groups in terms of cardiac electrophysiological parameters,serum norepinephrine levels,or LSG activity. After 30 days of IL-6 overexpression,the IL-6 group exhibited a significantly higher incidence of VA (P<0.05),along with a marked reduction in both QT and QTc intervals (P<0.05),as well as increased dispersion of both the QT and QTc intervals (P<0.05). Additionally,the IL-6 group showed significantly elevated serum norepinephrine levels and LSG activity compared to the control group,with a notable increase in synaptophysin density in the LSG (P<0.05).Conclusion Chronic overexpression of IL-6 in the LSG compromises cardiac electrophysiological stability and raises the incidence of VA,likely due to LSG remodeling-induced disruption of cardiac autonomic regulation

参考文献/References:

[1]Fukuda K,Kanazawa H,Aizawa Y,et al. Cardiac innervation and sudden cardiac death [J]. Circ Res,2015,116(12):2005-2019.

[2]Goldberger JJ,Arora R,Buckley U,et al. Autonomic nervous system dysfunction: JACC focus seminar [J]. J Am Coll Cardiol,2019,73(10):1189-1206.

[3]Deng J,Zhou X,Wang M,et al. The effects of interleukin 17A on left stellate ganglion remodeling are mediated by neuroimmune communication in normal structural hearts[J]. Int J cardiol ,2019,279:64-71.

[4]Wang M,Li S,Zhou X,et al. Increased inflammation promotes ventricular arrhythmia through aggravating left stellate ganglion remodeling in a canine ischemia model[J]. Int J Cardiol,2017,248:286-293.

[5]Yu L,Zhou L,Cao G,et al. Optogenetic modulation of cardiac?sympathetic nerve activity to?prevent ventricular?arrhythmias[J]. J Am Coll Cardiol,2017,70(22):2778-2790.

[6]Zhou L,Zhang Y,Cao G,et al. Wireless self-powered optogenetic system for long-term cardiac neuromodulation to improve post-mi cardiac remodeling and malignant arrhythmia[J]. Adv Sci (Weinh),2023,10(9):e2205551.

[7]Yu L,Wang Y,Zhou X,et al. Leptin injection into the left stellate ganglion augments ischemia-related ventricular arrhythmias via sympathetic nerve activation[J]. Heart Rhythm,2018,15(4):597-606.

[8]Jiao L,Wang Y,Zhang S,et al. Melatonin improves cardiac remodeling and brain-heart sympathetic hyperactivation aggravated by light disruption after myocardial infarction[J]. J Pineal Res,2022,73(4):e12829.

[9]Liu Z,Liu Z,Zhou H,et al. Increased sympathetic outflow induced by emotional stress aggravates myocardial ischemia-reperfusion injury via activation of TLR7/MyD88/IRF5 signaling pathway[J]. Inflamm Res,2023,72(5):901-913.

[10]Forcina L,Franceschi C,Musarò A. The hormetic and hermetic role of IL-6[J]. Ageing Res Rev,2022,80:101697.

[11]Zhang S,Wang M,Jiao L,et al. Ultrasound-guided injection of botulinum toxin type A blocks cardiac sympathetic ganglion to improve cardiac remodeling in a large animal model of chronic myocardial infarction[J]. Heart Rhythm,2022,19(12):2095-2104.

[12]Zelt JGE,deKemp RA,Rotstein BH,et al. Nuclear imaging of the cardiac sympathetic nervous system:a disease-specific interpretation in heart?failure[J]. JACC Cardiovasc Imaging,2020,13(4):1036-1054.

[13]Verrier RL,Antzelevitch C. Autonomic aspects of arrhythmogenesis:the enduring and the new[J]. Curr Opin in Cardiol,2004,19(1):2-11.

[14]Wallis D,Watson AH,Mo N. Cardiac neurones of autonomic ganglia[J]. Microsc Res Tech,1996,35(1):69-79.

[15]Mix E,Goertsches R,Zettl UK. Immunology and neurology[J]. J Neurol,2007,254(suppl 2):I12-117.

[16]Nakanishi M,Niidome T,Matsuda S,et al. Microglia-derived interleukin-6 and leukaemia inhibitory factor promote astrocytic differentiation of neural stem/progenitor cells [J]. Eur J Neurosci,2007,25(3):649-658.

[17]Zhang PL,Izrael M,Ainbinder E,et al. Increased myelinating capacity of embryonic stem cell derived oligodendrocyte precursors after treatment by interleukin-6/soluble interleukin-6 receptor fusion protein [J]. Mol Cell Neurosci,2006,31(3):387-398.

[18]Zhong J,Dietzel ID,Wahle P,et al. Sensory impairments and delayed regeneration of sensory axons in interleukin-6-deficient mice [J]. J Neurosci,1999,19(11):4305-4313.

[19]Cousin MA. Synaptophysin-dependent synaptobrevin-2 trafficking at the presynapse-Mechanism and function[J]. J Neurochem,2021,159(1):78-89.

更新日期/Last Update: 2025-07-31