[1]韩亚凡 汤宝鹏 王菲菲 孙华鑫 李瑶 桑婉玥 王璐 杨杭 周贤惠 芦颜美 张玲 李耀东.低强度耳屏迷走神经刺激通过减轻心房内质网应激缓解长程起搏诱导的心房颤动[J].心血管病学进展,2023,(5):470.[doi:10.16806/j.cnki.issn.1004-3934.2023.05.020]
　HAN Yafan,TANG Baopeng,WANG Feifei,et al.Transcutaneous Auricular Vagus Nerve Stimulation Relieves Long-Term Pacing-Induced Atrial Fibrillation by Reducing Atrial Endoplasmic Reticulum Stress[J].Advances in Cardiovascular Diseases,2023,(5):470.[doi:10.16806/j.cnki.issn.1004-3934.2023.05.020]
点击复制

低强度耳屏迷走神经刺激通过减轻心房内质网应激缓解长程起搏诱导的心房颤动()
分享到：

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

卷:
期数:
2023年5期
页码:
470
栏目:
论著
出版日期:
2023-05-25

文章信息/Info

Title:
Transcutaneous Auricular Vagus Nerve Stimulation Relieves Long-Term Pacing-Induced Atrial Fibrillation by Reducing Atrial Endoplasmic Reticulum Stress
作者:
韩亚凡1 汤宝鹏 1 王菲菲 1 孙华鑫 1 李瑶 2 桑婉玥 1 王璐 1 杨杭1 周贤惠 1 芦颜美 1 张玲 1 李耀东 1
(1.新疆医科大学第一附属医院心脏中心起搏电生理科 新疆心电生理与心脏重塑重点实验室,新疆 乌鲁木齐 830054;2.成都市第四人民医院心身医学中心,四川 成都 610000)
Author(s):
HAN Yafan1; TANG Baopeng1; WANG Feifei1; SUN Huaxin1; LI Yao2; SANG Wanyue1; WANG Lu1; YANG Hang1; ZHOU Xianhui1; LU Yanmei1; ZHANG Ling1; LI Yaodong1
(1.Department of Pacing and Electrophysiology,Department of Cardiac Electrophysiology and Remodeling,The First Affiliated Hospital of Xinjiang Medical University,Urumqi 830054,China; 2.Center of Psychosomatic Medicine,The Fourth Peoples Hospital of Chengdu,Chengdu 610000,Sichuan,China)
关键词:
心房颤动; 迷走神经刺激; 自主神经; 内质网应激; 凋亡
Keywords:
Atrial fibrillation; Vagus nerve stimulation; Autonomic nerve; Endoplasmic reticulum stress; Apoptosis
DOI:
10.16806/j.cnki.issn.1004-3934.2023.05.020
摘要:
目的 探讨低强度耳屏迷走神经刺激（ta-VNS）在长程起搏诱导的心房颤动（Af）犬模型中的作用及潜在机制。方法 18只成年健康Beagle犬随机分为三组：假手术组、Af组和Af+ta-VNS组。所有犬均植入右心房快速起搏器，除假手术组不起搏外其余组给予600次/min参数起搏，持续4周。Af+ta-VNS组于第4周末给予ta-VNS直至第8周末，其余组给予假刺激。所有实验犬分别于基线期、4周末、8周末采集静脉血检测血清乙酰胆碱、肾上腺素及去甲肾上腺素浓度；评估左/右房内径和左室射血分数；检测心房有效不应期、Af易损窗、Af诱发率及Af平均持续时间等电生理指标。实验结束后取心房组织行TUNEL染色并检测GRP78、PERK、p-PERK、eIF2α、p-eIF2α、CHOP等内质网应激相关蛋白表达水平。结果 血清学检测显示Af+ta-VNS组血清乙酰胆碱水平升高，肾上腺素及去甲肾上腺素水平降低（P＜0.05）。在体电生理检测显示，ta-VNS可有效降低Af模型犬的Af易损窗、Af诱发率及Af持续时间并恢复心房有效不应期（P＜0.05）；同时ta-VNS可有效缩小左/右心房内径、降低心率并恢复射血分数（P＜0.05）。分子生物学检测显示，Af+ta-VNS组可有效减少心房肌细胞凋亡，并降低GRP78、PERK、p-PERK、eIF2α、p-eIF2α、CHOP等内质网应激相关蛋白表达水平（P＜0.05）。结论 ta-VNS可通过抑制内质网应激及心肌细胞凋亡，减轻长程起搏诱导的心房重塑。
Abstract:
Objective To investigate the effect and potential mechanism of transcutaneous auricular vagus nerve stimulation(ta-VNS) on long-term pacing-induced atrial fibrillation(Af) in dog models. Methods Eighteen healthy adult Beagle dogs were randomly divided into three groups:sham-operated group, Af group and Af+ta-VNS group. All dogs were implanted with rapid pacemakers in the right atrium. Except the sham-operated group,the other groups were given 600 beats/min pacing for 4 weeks. The Af+ta-VNS group was given ta-VNS after 4 weeks until the end of 8 th week,while the other groups were given sham stimulation. Venous blood was collected from all experimental dogs at the baseline period,the end of the 4th week and the end of the 8th week to detect the concentration of serum acetylcholine,epinephrine and norepinephrine. Left/right atrial diameters and left ventricular ejection fraction were evaluated. Electrophysiological indexes such as the atrial effective refractory period,vulnerable window of Af,induction rate of Af and average duration of Af were detected. At the end of the experiment,th e atrial tissue was taken for TUNEL staining and the expression levels of endoplasmic reticulum stress(ERS) related proteins such as GRP78,PERK,p-P ERK,eIF2α,p-eIF2α and CHOP were detected. Results Serological examination showed that the serum acetylcholine level increased and the serum epinephrine and norepinephrine levels decreased in Af+ta-VNS group(P<0.05). In vivo electrophysiological examination showed that ta-VNS could effectively reduce vulnerable window of Af,Af induction rate,duration of Af and restore atrial effective refractory period in dogs with Af(P<0.05). At the same time,ta-VNS can effectively reduce the left/right atrial diameter,reduce heart rate and restore ejection fraction(P<0.05). Molecular biological analysis showed that Af+ta-VNS could effectively reduce the apoptosis of atrial myocytes and the expression of GRP78,PERK,p-PERK,eIF2α,p-eIF2α,CHOP and other ERS related proteins(P<0.05). Conclusion ta-VNS can reduce long-term pacing induced Af by inhibiting ERS and cardiomyocyte apoptosis.

参考文献/References:

[1] Wijesurendra RS,Casadei B. Mechanisms of atrial fibrillation[J]. Heart,2019,105(24):1860-1867.

[2] Sagris M,Vardas EP,Theofilis P,et al. Atrial fibrillation:pathogenesis,predisposing factors,and genetics[J]. Int J Mol Sci,2021,23(1):6.

[3] Brundel BJJM,Ai X,Hills MT,et al. Atrial fibrillation[J]. Nat Rev Dis Primers,2022,8(1):21.

[4] Armbruster AL,Campbell KB,Kahanda MG,et al. The role of inflammation in the pathogenesis and treatment of arrhythmias[J]. Pharmacotherapy,2022,42(3):250-262.

[5] Chou RH,Lo LW,Leu HB. Autonomic dysfunction plays a decisive role in the arrhythmia initiation,whereas metabolic disorders facilitate further atrial remodeling in antipsychotic-related atrial fibrillation[J]. Int J Cardiol,2017,247:33.

[6] Qi Z,Chen L. Endoplasmic reticulum stress and autophagy[J]. Adv Exp Med Biol,2019,1206:167-177.

[7] Yarmohammadi F,Hayes AW,Karimi G. Possible protective effect of resolvin D1 on inflammation in atrial fibrillation:involvement of ER stress mediated the NLRP3 inflammasome pathway[J]. Naunyn Schmiedebergs Arch Pharmacol,2021,394 (8):1613-1619.

[8] Ren J,Bi Y,Sowers JR,et al. Endoplasmic reticulum stress and unfolded protein response in cardiovascular diseases[J]. Nat Rev Cardiol,2021,18(7):499-521.

[9] Tse G,Yan BP,Chan YW,et al. Reactive oxygen species,endoplasmic reticulum stress and mitochondrial dysfunction:the link with cardiac arrhythmogenesis[J]. Front Physiol,2016,7:313.

[10] Miao W,Shi J,Huang J,et al. Azoramide ameliorated tachypacing-induced injury of atrial myocytes differentiated from human induced pluripotent stem cell by regulating endoplasmic reticulum stress[J]. Stem Cell Res,2022,60:102686.

[11] Sirish P,Diloretto DA,Thai PN,et al. The critical roles of proteostasis and endoplasmic reticulum stress in atrial fibrillation[J]. Front Physiol,2021,12:793171.

[12] Nasi-Er BG,Wenhui Z,HuaXin S,et al. Vagus nerve stimulation reduces ventricular arrhythmias and increases ventricular electrical stability[J]. Pacing Clin Electrophysiol,2019,42(2):247-256.

[13] Sun H,Nasi-Er BG,Wang X,et al. Tragus nerve stimulation suppresses post-infarction ventricular arrhythmia by modulating autonomic activity and heterogeneities of cardiac receptor distribution[J]. Med Sci Monit,2020,26:e922277.

[14] Guo Y,Xiaokereti J,Meng Q,et al. Low-level vagus nerve stimulation reverses obstructive sleep apnea-related atrial fibrillation by ameliorating sympathetic hyperactivity and atrial myocyte injury[J]. Front Physiol,2020,11:620655.

[15] Dalal S,Foster CR,Das BC,et al. Β-adrenergic receptor stimulation induces endoplasmic reticulum stress in adult cardiac myocytes:role in apoptosis[J]. Mol Cell Biochem,2012,364(1-2):59-70.

[16] Mottillo EP,Shen XJ,Granneman JG. Beta3-adrenergic receptor induction of adipocyte inflammation requires lipolytic activation of stress kinases p38 and JNK[J]. Biochim Biophys Acta,2010,1801(9):1048-1055.

[17] Manolis AA,Manolis TA,Apostolopoulos EJ,et al. The role of the autonomic nervous system in cardiac arrhythmias:the neuro-cardiac axis,more foe than friend?[J]. Trends Cardiovasc Med,2021,31(5):290-302.

[18] Abdullahi A,Wang V,Auger C,et al. Catecholamines induce endoplasmic reticulum stress via both alpha and beta receptors[J]. Shock,2020,53(4):476-484.

[19] Linz D,Elliott AD,Hohl M,et al. Role of autonomic nervous system in atrial fibrillation[J]. Int J Cardiol,2019,287:181-188.

[20] Hanna P,Buch E,Stavrakis S,et al. Neuroscientific therapies for atrial fibrillation[J]. Cardiovasc Res,2021,117(7):1732-1745.

[21] Carandina A,Rodrigues GD,di Francesco P,et al. Effects of transcutaneous auricular vagus nerve stimulation on cardiovascular autonomic control in health and disease[J]. Auton Neurosci,2021,236:102893.

[22] Zafeiropoulos S,Doundoulakis I,Farmakis IT,et al. Autonomic neuromodulation for atrial fibrillation following cardiac surgery:JACC review topic of the week[J]. J Am Coll Cardiol,2022,79(7):682-694.

[23] Huang B,Liu H,Scherlag BJ,et al. Atrial fibrillation in obstructive sleep apnea:neural mechanisms and emerging therapies[J]. Trends Cardiovasc Med,2021,31(2):127-132.

[24] Kulkarni K,Singh JP,Parks KA,et al. Low-level tragus stimulation modulates atrial alternans and fibrillation burden in patients with paroxysmal atrial fibrillation[J]. J Am Heart Assoc,2021,10(12):e020865.

[25] Stavrakis S,Stoner JA,Humphrey MB,et al. TREAT AF(Transcutaneous Electrical Vagus Nerve Stimulation to Suppress Atrial Fibrillation):a randomized clinical trial[J]. JACC Clin Electrophysiol,2020,6(3):282-291.

相似文献/References:

[1]贺鹏康,周菁.心房颤动治疗新技术——冷冻球囊消融[J].心血管病学进展,2016,(1):1.[doi:10.16806/j.cnki.issn.1004-3934.2016.01.001]
　HE Pengkang,ZHOU Jing.Cryoballoon Ablation, A Novel Technology for Atrial Fibrillation Treatment[J].Advances in Cardiovascular Diseases,2016,(5):1.[doi:10.16806/j.cnki.issn.1004-3934.2016.01.001]
[2]都明辉,施海峰*,佟佳宾,等.心房颤动消融相关性无症状性脑缺血[J].心血管病学进展,2016,(1):3.[doi:10.16806/j.cnki.issn.1004-3934.2016.01.002]
　DU Minghui,SHI Haifeng*,TONG Jiabin,et al.Silent Cerebral Ischemia Related to Atrial Fibrillation Ablation[J].Advances in Cardiovascular Diseases,2016,(5):3.[doi:10.16806/j.cnki.issn.1004-3934.2016.01.002]
[3]郑环杰,综述,肖骅,等.心房颤动抗栓治疗研究进展[J].心血管病学进展,2016,(2):142.[doi:10.16806/j.cnki.issn.1004-3934.2016.02.012]
　ZHENG Huanjie,XIAO Hua.Progress of Antithrombotic Therapy in Patients with Atrial Fibrillation[J].Advances in Cardiovascular Diseases,2016,(5):142.[doi:10.16806/j.cnki.issn.1004-3934.2016.02.012]
[4]张清,综述,罗素新,等.新型Xa 因子抑制剂———依度沙班在心房颤动患者抗凝治疗中的研究进展[J].心血管病学进展,2016,(2):151.[doi:10.16806/j.cnki.issn.1004-3934.2016.02.014]
　ZHANG Qing,LUO Suxin,TANG Jiong.Novel Factor Xa Inhibitors—Edoxaban in Prevention of Stroke in Patients with Atrial Fibrillation[J].Advances in Cardiovascular Diseases,2016,(5):151.[doi:10.16806/j.cnki.issn.1004-3934.2016.02.014]
[5]胡红玲,综述,罗素新,等.预防非瓣膜性心房颤动性脑卒中的治疗新进展[J].心血管病学进展,2016,(3):250.[doi:10.16806/j.cnki.issn.1004-3934.2016.03.009]
　HU Hongling,LUO Suxin.New Progress in the Treatment for Cerebral Apoplexy of Nonvalvular Atrial Fibrillation[J].Advances in Cardiovascular Diseases,2016,(5):250.[doi:10.16806/j.cnki.issn.1004-3934.2016.03.009]
[6]王超,杨国澍,综述,等.关附甲素治疗心房颤动的研究进展[J].心血管病学进展,2016,(3):254.[doi:10.16806/j.cnki.issn.1004-3934.2016.03.010]
　WANG Chao,YANG Guoshu,CAI Lin,et al.Research Progress of the Treatment of Atrial Fibrillation[J].Advances in Cardiovascular Diseases,2016,(5):254.[doi:10.16806/j.cnki.issn.1004-3934.2016.03.010]
[7]徐小东,综述,杨东辉,等.决奈达隆治疗心房颤动的现状及展望[J].心血管病学进展,2016,(4):368.[doi:10.16806/j.cnki.issn.1004-3934.2016.04.011]
　XU Xiaodong,YANG Donghui.Status and Prospect of Dronedarone in Treating Atrial Fibrillation[J].Advances in Cardiovascular Diseases,2016,(5):368.[doi:10.16806/j.cnki.issn.1004-3934.2016.04.011]
[8]张莎,储国俊,吴弘.经导管左心耳封堵术的临床应用进展[J].心血管病学进展,2015,(5):547.[doi:10.3969/j.issn.1004-3934.2015.05.006]
　ZHANG Sha,CHU Guojun,WU Hong.Clinial Application Advances in Left Atrial Appendage Closure[J].Advances in Cardiovascular Diseases,2015,(5):547.[doi:10.3969/j.issn.1004-3934.2015.05.006]
[9]汪俊,杨浩.心房颤动射频消融的术式演变[J].心血管病学进展,2015,(5):574.[doi:10.3969/j.issn.1004-3934.2015.05.013]
　WANG Jun,YANG Hao.Evolution of Radiofrequency Ablation of Atrial Fibrillation[J].Advances in Cardiovascular Diseases,2015,(5):574.[doi:10.3969/j.issn.1004-3934.2015.05.013]
[10]赵璐,苏立.心房颤动与离子通道重构研究进展[J].心血管病学进展,2015,(5):580.[doi:10.3969/j.issn.1004-3934.2015.05.014]
　ZHAO Lu,SU Li.Research Progress of Atrial Fibrillation and Ion Channel Remodeling[J].Advances in Cardiovascular Diseases,2015,(5):580.[doi:10.3969/j.issn.1004-3934.2015.05.014]

更新日期/Last Update: 2023-06-29