迷走神经刺激在慢性心力衰竭炎症及凋亡机制中的应用研究进展

doi:10.12114/j.issn.1007-9572.2023.0693

摘要/Abstract

摘要： 心迷走神经作为心脏自主神经系统重要的神经，对于慢性心力衰竭的治疗有着重要的作用。近年来，多个研究发现迷走神经刺激通过减少炎性因子及相关蛋白的表达、凋亡相关蛋白的表达，来改善心肌功能及心室重塑等，从而对心脏功能进行保护，延缓慢性心力衰竭的进展。然而，关于迷走神经在慢性心力衰竭炎症及凋亡机制的相关报道较少，因此本文综述了心迷走神经的解剖、治疗的可能机制、迷走神经刺激实用参数以及近年来有关迷走神经刺激在慢性心力衰竭炎症和凋亡机制中的应用和最新临床进展，为后续相关研究开展提供借鉴。

关键词: 心力衰竭, 迷走神经刺激术, 慢性心力衰竭, 炎症, 凋亡, 综述

Abstract:

As a crucial component of the cardiac autonomic nervous system, the cardiac vagus nerve plays a significant role in the management of chronic heart failure. In recent years, several studies have found that vagus nerve stimulation protects cardiac function and delays the progression of chronic heart failure by reducing the expression of inflammatory factors and related proteins, apoptosis-related proteins, and improving myocardial function and ventricular remodeling. However, there are limited reports related to the mechanism of inflammation and apoptosis of the vagus nerve in chronic heart failure. Hence, this article reviews the anatomy of the cardiac vagus nerve, potential treatment mechanisms, practical parameters of vagus nerve stimulation, and the recent applications and clinical progress of vagus nerve stimulation in inflammation and apoptosis mechanisms in chronic heart failure, in order to provide a reference for the future related research.

Key words: Heart failure, Vagus nerve stimulation, Chronic heart failure, Inflammation, Apoptosis, Review

中图分类号:

R 541.62

胡宇驰,代松源,赵玲,等. 迷走神经刺激在慢性心力衰竭炎症及凋亡机制中的应用研究进展[J]. 中国全科医学, 2024, 27(24): 3044-3050. DOI: 10.12114/j.issn.1007-9572.2023.0693.
HU Yuchi,DAI Songyuan,ZHAO Ling, et al. Advances in the Application of Vagus Nerve Stimulation in Inflammation and Apoptosis Mechanism of Chronic Heart Failure[J]. Chinese General Practice, 2024, 27(24): 3044-3050. DOI: 10.12114/j.issn.1007-9572.2023.0693.

参考文献 42

[1]	张永珍，范媛媛. 心力衰竭通用定义和分类解读[J]. 中国心血管杂志，2021，26（5）：409-412. DOI：10.3969/j.issn.1007-5410.2021.05.001.
[2]	MARTIN N，MANOHARAN K，DAVIES C，et al. Beta-blockers and inhibitors of the renin-angiotensin aldosterone system for chronic heart failure with preserved ejection fraction[J]. Cochrane Database Syst Rev，2021，5（5）：CD012721. DOI：10.1002/14651858.CD012721.pub3.
[3]	ANAND I S，KONSTAM M A，KLEIN H U，et al. Comparison of symptomatic and functional responses to vagus nerve stimulation in ANTHEM-HF，INOVATE-HF，and NECTAR-HF[J]. ESC Heart Fail，2020，7（1）：75-83. DOI：10.1002/ehf2.12592.
[4]	ARIMURA T，SAKU K，KAKINO T，et al. Intravenous electrical vagal nerve stimulation prior to coronary reperfusion in a canine ischemia-reperfusion model markedly reduces infarct size and prevents subsequent heart failure[J]. Int J Cardiol，2017，227：704-710. DOI：10.1016/j.ijcard.2016.10.074.
[5]	DICARLO L A，LIBBUS I，KUMAR H U，et al. Autonomic regulation therapy to enhance myocardial function in heart failure patients：the ANTHEM-HFpEF study[J]. ESC Heart Fail，2018，5（1）：95-100. DOI：10.1002/ehf2.12241.
[6]	SANT'ANNA L B，COUCEIRO S L M，FERREIRA E A，et al. Vagal neuromodulation in chronic heart failure with reduced ejection fraction：a systematic review and meta-analysis[J]. Front Cardiovasc Med，2021，8：766676. DOI：10.3389/fcvm.2021.766676.
[7]	HADAYA J，ARDELL J L. Autonomic modulation for cardiovascular disease[J]. Front Physiol，2020，11：617459. DOI：10.3389/fphys.2020.617459.
[8]	SHARMA K，PREMCHAND R K，MITTAL S，et al. Long-term follow-up of patients with heart failure and reduced ejection fraction receiving autonomic regulation therapy in the ANTHEM-HF pilot study[J]. Int J Cardiol，2021，323：175-178. DOI：10.1016/j.ijcard.2020.09.072.
[9]	OTTAVIANI M M，MACEFIELD V G. Structure and functions of the vagus nerve in mammals[J]. Compr Physiol，2022，12（4）：3989-4037. DOI：10.1002/cphy.c210042.
[10]	SHAFFER C，BARRETT L F，QUIGLEY K S. Signal processing in the vagus nerve：hypotheses based on new genetic and anatomical evidence[J]. Biol Psychol，2023，182：108626. DOI：10.1016/j.biopsycho.2023.108626.
[11]	薛松维. 心力衰竭非药物治疗之无创迷走神经刺激术（55）[J]. 中国乡村医药，2019，26（17）：27-28. DOI：10.19542/j.cnki.1006-5180.003199.
[12]	DOLPHIN H，DUKELOW T，FINUCANE C，et al. ＂The wandering nerve linking heart and mind＂-the complementary role of transcutaneous vagus nerve stimulation in modulating neuro-cardiovascular and cognitive performance[J]. Front Neurosci，2022，16：897303. DOI：10.3389/fnins.2022.897303.
[13]	CARAVACA A S，GALLINA A L，TARNAWSKI L，et al. Vagus nerve stimulation promotes resolution of inflammation by a mechanism that involves Alox15 and requires the α7nAChR subunit[J]. Proc Natl Acad Sci USA，2022，119（22）：e2023285119. DOI：10.1073/pnas.2023285119.
[14]	STAVRAKIS S，ELKHOLEY K，MORRIS L，et al. Neuromodulation of inflammation to treat heart failure with preserved ejection fraction：a pilot randomized clinical trial[J]. J Am Heart Assoc，2022，11（3）：e023582. DOI：10.1161/JAHA.121.023582.
[15]	SABBAH H N，ILSAR I，ZARETSKY A，et al. Vagus nerve stimulation in experimental heart failure[J]. Heart Fail Rev，2011，16（2）：171-178. DOI：10.1007/s10741-010-9209-z.
[16]	ALLEN E，PONGPAOPATTANAKUL P，CHAUHAN R A，et al. The effects of vagus nerve stimulation on ventricular electrophysiology and nitric oxide release in the rabbit heart[J]. Front Physiol，2022，13：867705. DOI：10.3389/fphys.2022.867705.
[17]	YANCY C W，JESSUP M，BOZKURT B，et al. 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure：A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America[J]. Circulation，2017，136（6）：e137-161. DOI：10.1161/CIR.0000000000000509.
[18]	COOPER C M，FARRAND A Q，ANDRESEN M C，et al. Vagus nerve stimulation activates nucleus of solitary tract neurons via supramedullary pathways[J]. J Physiol，2021，599（23）：5261-5279. DOI：10.1113/JP282064.
[19]	MARTLÉ V，VAN HAM L M，BOON P，et al. Vagus nerve stimulator placement in dogs：surgical implantation technique，complications，long-term follow-up，and practical considerations[J]. Vet Surg，2016，45（1）：71-78. DOI：10.1111/vsu.12427.
[20]	HARCOURT-BROWN T R，CARTER M. Implantable vagus nerve stimulator settings and short-term adverse effects in epileptic dogs[J]. J Vet Intern Med，2021，35（5）：2350-2358. DOI：10.1111/jvim.16226.
[21]	LI Y，XUAN Y H，LIU S S，et al. Short-term vagal nerve stimulation improves left ventricular function following chronic heart failure in rats[J]. Mol Med Rep，2015，12（2）：1709-1716. DOI：10.3892/mmr.2015.3597.
[22]	DE FERRARI G M，STOLEN C，TUINENBURG A E，et al. Long-term vagal stimulation for heart failure：eighteen month results from the NEural Cardiac TherApy foR Heart Failure（NECTAR-HF）trial[J]. Int J Cardiol，2017，244：229-234. DOI：10.1016/j.ijcard.2017.06.036.
[23]	ZHOU L P，FILIBERTI A，HUMPHREY M B，et al. Low-level transcutaneous vagus nerve stimulation attenuates cardiac remodelling in a rat model of heart failure with preserved ejection fraction[J]. Exp Physiol，2019，104（1）：28-38. DOI：10.1113/EP087351.
[24]	赵利，苏玮，王坤，等. 经皮迷走神经耳支刺激改善心力衰竭犬的心功能研究[J]. 医学信息，2020，33（11）：58-60，71. DOI：10.3969/j.issn.1006-1959.2020.11.018.
[25]	HOU B，WANG D D，QIU Y H，et al. Boosting NAD level suppresses inflammatory activation of PBMCs in heart failure[J]. J Clin Invest，2020，130（11）：6054-6063. DOI：10.1172/JCI138538.
[26]	LUO B，WU Y，LIU S L，et al. Vagus nerve stimulation optimized cardiomyocyte phenotype，sarcomere organization and energy metabolism in infarcted heart through FoxO3A-VEGF signaling[J]. Cell Death Dis，2020，11（11）：971. DOI：10.1038/s41419-020-03142-0.
[27]	SUN Y，CHAO S Y，OUYANG H，et al. Hybrid nanogenerator based closed-loop self-powered low-level vagus nerve stimulation system for atrial fibrillation treatment[J]. Sci Bull，2022，67（12）：1284-1294. DOI：10.1016/j.scib.2022.04.002.
[28]	XUAN Y H，LIU S S，LI Y，et al. Short-term vagus nerve stimulation reduces myocardial apoptosis by downregulating microRNA-205 in rats with chronic heart failure[J]. Mol Med Rep，2017，16（5）：5847-5854. DOI：10.3892/mmr.2017.7344.
[29]	WANG Y，ZHANG Y. LncRNA CAIF suppresses LPS-induced inflammation and apoptosis of cardiomyocytes through regulating miR-16 demethylation[J]. Immun Inflamm Dis，2021，9（4）：1468-1478. DOI：10.1002/iid3.498.
[30]	ZHANG X Y，GAO Y K，WU H Y，et al. LncRNA HOX transcript antisense RNA mitigates cardiac function injury in chronic heart failure via regulating microRNA-30a-5p to target KDM3A[J]. J Cell Mol Med，2022，26（5）：1473-1485. DOI：10.1111/jcmm.17160.
[31]	FENG Y L，YAN B，CHENG H J，et al. Knockdown circ_0040414 inhibits inflammation，apoptosis and promotes the proliferation of cardiomyocytes via miR-186-5p/PTEN/AKT axis in chronic heart failure[J]. Cell Biol Int，2021，45（11）：2304-2315. DOI：10.1002/cbin.11678.
[32]	LI T，QIAN D，GUOYAN J，et al. Downregulated long noncoding RNA LUCAT1 inhibited proliferation and promoted apoptosis of cardiomyocyte via miR-612/HOXA13 pathway in chronic heart failure[J]. Eur Rev Med Pharmacol Sci，2020，24（1）：385-395. DOI：10.26355/eurrev_202001_19937.
[33]	BEAUMONT E，SOUTHERLAND E M，HARDWICK J C，et al. Vagus nerve stimulation mitigates intrinsic cardiac neuronal and adverse myocyte remodeling postmyocardial infarction[J]. Am J Physiol Heart Circ Physiol，2015，309（7）：H1198-1206. DOI：10.1152/ajpheart.00393.2015.
[34]	张秀，程怡慧，张心彤，等. 生理性缺血训练改善心肌梗死后慢性心力衰竭大鼠心功能及心室重塑的神经机制[J]. 中国康复医学杂志，2021，36（8）：915-922. DOI：10.3969/j.issn.1001-1242.2021.08.003.
[35]	NEARING B D，LIBBUS I，CARLSON G M，et al. Chronic vagus nerve stimulation is associated with multi-year improvement in intrinsic heart rate recovery and left ventricular ejection fraction in ANTHEM-HF[J]. Clin Auton Res，2021，31（3）：453-462. DOI：10.1007/s10286-021-00780-y.
[36]	KONSTAM M A，MANN D L，UDELSON J J E，et al. Advances in our clinical understanding of autonomic regulation therapy using vagal nerve stimulation in patients living with heart failure[J]. Front Physiol，2022，13：857538. DOI：10.3389/fphys.2022.857538.
[37]	KUMAR H U，NEARING B D，MITTAL S，et al. Autonomic regulation therapy in chronic heart failure with preserved/mildly reduced ejection fraction：anthem-HFpEF study results[J]. Int J Cardiol，2023，381：37-44. DOI：10.1016/j.ijcard.2023.03.030.
[38]	WANG H，SHI J J，SHI S Q，et al. Bibliometric analysis on the progress of chronic heart failure[J]. Curr Probl Cardiol，2022，47（9）：101213. DOI：10.1016/j.cpcardiol.2022.101213.
[39]	VERRIER R L，LIBBUS I，NEARING B D，et al. Multifactorial benefits of chronic vagus nerve stimulation on autonomic function and cardiac electrical stability in heart failure patients with reduced ejection fraction[J]. Front Physiol，2022，13：855756. DOI：10.3389/fphys.2022.855756.
[40]	ELAMIN A B A，FORSAT K，SENOK S S，et al. Vagus nerve stimulation and its cardioprotective abilities：a systematic review[J]. J Clin Med，2023，12（5）：1717. DOI：10.3390/jcm12051717.
[41]	DU Z Y，WANG J L，LU Y Y，et al. The cardiac protection of Baoyuan Decoction via gut-heart axis metabolic pathway[J]. Phytomedicine，2020，79：153322. DOI：10.1016/j.phymed.2020.153322.
[42]	SUN W J，DU D B，FU T Z，et al. Alterations of the gut microbiota in patients with severe chronic heart failure[J]. Front Microbiol，2022，12：813289. DOI：10.3389/fmicb.2021.813289.