心肌梗死后交感神经重构的研究进展及其法医学意义
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摘要
心肌梗死后交感神经重构表现为去神经支配、交感神经芽生及交感神经分布密度增高,与心肌梗死患者恢复期发生室性快速心律失常甚至心脏性猝死密切相关。本文综述了心脏交感神经解剖结构、交感神经形态和功能重构及其在陈旧性心肌梗死鉴定中的作用,以期为法医学研究提供参考。
Sympathetic remodeling after myocardial infarction is presented as denervation, sympathetic nerve sprouting and sympathetic hyperinnervation, and is closely related to ventricular tachyarrhythmias and even sudden cardiac death at convalescence in patients with myocardial infarction. This article reviews the anatomic structure, morphology and functional remodeling of cardiac sympathetic nerve, as well as its role in healed myocardial infarction identification, which may provide references for forensic research.
Sympathetic remodeling after myocardial infarction is presented as denervation, sympathetic nerve sprouting and sympathetic hyperinnervation, and is closely related to ventricular tachyarrhythmias and even sudden cardiac death at convalescence in patients with myocardial infarction. This article reviews the anatomic structure, morphology and functional remodeling of cardiac sympathetic nerve, as well as its role in healed myocardial infarction identification, which may provide references for forensic research.
引文
[1]DAMBRINK J H,SIPPENSGROENEWEGEN A,VAN GILST W H,et al.Association of left ventricular remodeling and nonuniform electrical recovery expressed by nondipolar QRST integral map patterns in survivors of a first anterior myocardial infarction.Captopril and thrombolysis study investigators[J].Circulation,1995,92(3):300-310.
[2]LUO D,HU H,QIN Z,et al.Stimulation of ganglionated plexus attenuates cardiac neural remodeling and heart failure progression in a canine model of acute heart failure post-myocardial infarction[J].Auton Neurosci,2017,208:73-79.
[3]D’ELIA E,PASCALE A,MARCHESI N,et al.Novel approaches to the post-myocardial infarction/heart failure neural remodeling[J].Heart Fail Rev,2014,19(5):611-619.
[4]CAO J M,FISHBEIN M C,HAN J B,et al.Relationship between regional cardiac hyperinnervation and ventricular arrhythmia[J].Circulation,2000,101(16):1960-1969.
[5]CAO J M,CHEN L S,KENKNIGHT B H,et al.Nerve sprouting and sudden cardiac death[J].Circ Res,2000,86(7):816-821.
[6]WANG Y,XUAN Y L,HU H S,et al.Risk of ventricular arrhythmias after myocardial infarction with diabetes associated with sympathetic neural remodeling in rabbits[J].Cardiology,2012,121(1):1-9.
[7]CHEN P S,CHEN L S,CAO J M,et al.Sympathetic nerve sprouting,electrical remodeling and the mechanisms of sudden cardiac death[J].Cardiovasc Res,2001,50(2):409-416.
[8]GUYENET P G.The sympathetic control of blood pressure[J].Nat Rev Neurosci,2006,7(5):335-346.
[9]TAN A Y,VERRIER R L.The role of the autonomic nervous system in cardiac arrhythmias[J].Handb Clin Neurol,2013,117:135-145.
[10]VRACKO R,THORNING D,FREDERICKSON RG.Fate of nerve fibers in necrotic,healing,and healed rat myocardium[J].Lab Invest,1990,63(4):490-501.
[11]NORI S L,GAUDINO M,ALESSANDRINI F,et al.Immunohistochemical evidence for sympathetic denervation and reinnervation after necrotic injury in rat myocardium[J].Cell Mol Biol(Noisy-le-grand),1995,41(6):799-807.
[12]FALLEN E L,COATES G,NAHMIAS C,et al.Recovery rates of regional sympathetic reinnervation and myocardial blood flow after acute myocardial infarction[J].Am Heart J,1999,137(5):863-869.
[13]CHEN Z L,YU W M,STRICKLAND S.Peripheral regeneration[J].Annu Rev Neurosci,2007,30:209-233.
[14]JESSEN K R,MIRSKY R.Negative regulation of myelination:relevance for development,injury,and demyelinating disease[J].Glia,2008,56(14):1552-1565.
[15]FONTANA X,HRISTOVA M,DA COSTA C,et al.c-Jun in Schwann cells promotes axonal regeneration and motoneuron survival via paracrine signaling[J].J Cell Biol,2012,198(1):127-141.
[16]BRUSHART T M,ASPALTER M,GRIFFIN J W,et al.Schwann cell phenotype is regulated by axon modality and central-peripheral location,and persists in vitro[J].Exp Neurol,2013,247:272-281.
[17]WOOD M D,MACKINNON S E.Pathways regulating modality-specific axonal regeneration in peripheral nerve[J].Exp Neurol,2015,265:171-175.
[18]SCHEIB J,H?KE A.Advances in peripheral nerve regeneration[J].Nat Rev Neurol,2013,9(12):668-676.
[19]MARTINI R,FISCHER S,LóPEZ-VALES R,et al.Interactions between Schwann cells and macrophages in injury and inherited demyelinating disease[J].Glia,2008,56(14):1566-1577.
[20]ROTSHENKER S.Wallerian degeneration:the innate-immune response to traumatic nerve injury[J].J Neuroinflammation,2011,8:109.
[21]CAFFERTY W B,GARDINER N J,GAVAZZI I,et al.Leukemia inhibitory factor determines the growth status of injured adult sensory neurons[J].J Neurosci,2001,21(18):7161-7170.
[22]BAUER S,KERR B J,PATTERSON P H.The neuropoietic cytokine family in development,plasticity,disease and injury[J].Nat Rev Neurosci,2007,8(3):221-232.
[23]BARRETTE B,HéBERT M A,FILALI M,et al.Requirement of myeloid cells for axon regeneration[J].J Neurosci,2008,28(38):9363-9376.
[24]NIEMI J P,DEFRANCESCO-LISOWITZ A,ROLDáN-HERNáNDEZ L,et al.A critical role for macrophages near axotomized neuronal cell bodies in stimulating nerve regeneration[J].J Neurosci,2013,33(41):16236-16248.
[25]CATTIN A L,BURDEN J J,van EMMENISL,et al.Macrophage-induced blood vessels guide Schwann cell-mediated regeneration of peripheral nerves[J].Cell,2015,162(5):1127-1139.
[26]DUBOVY P,JANCáLEK R,KUBEK T.Role of inflammation and cytokines in peripheral nerve regeneration[J].Int Rev Neurobiol,2013,108:173-206.
[27]EMANUELE E,POLITI P,BIANCHI M,et al.Raised plasma nerve growth factor levels associated with early-stage romantic love[J].Psychoneuroendocrinology,2006,31(3):288-294.
[28]MIAS C,COATRIEUX C,DENIS C,et al.Cardiac fibroblasts regulate sympathetic nerve sprouting and neurocardiac synapse stability[J].PLoS One,2013,8(11):e79068.
[29]WERNLI G,HASAN W,BHATTACHERJEE A,et al.Macrophage depletion suppresses sympathetic hyperinnervation following myocardial infarction[J].Basic Res Cardiol,2009,104(6):681-693.
[30]ZHANG H,YUAN X,JIN P F,et al.Alteration of parasympathetic/sympathetic ratio in the infarcted myocardium after Schwann cell transplantation modified electrophysiological function of heart:a novel antiarrhythmic therapy[J].Circulation,2010,122(S11):S193-S200.
[31]ZHOU L,TOO H P.Mitochondrial localized STAT3is involved in NGF induced neurite outgrowth[J].PLoS One,2011,6(6):e21680.
[32]PELLEGRINO M J,HABECKER B A.STAT3 integrates cytokine and neurotrophin signals to promote sympathetic axon regeneration[J].Mol Cell Neurosci,2013,56:272-282.
[33]BEN-YAAKOV K,DAGAN S Y,SEGAL-RUDERY,et al.Axonal transcription factors signal retrogradely in lesioned peripheral nerve[J].Embo J,2012,31(6):1350-1363.
[34]EHLERS M D,KAPLAN D R,PRICE D L,et al.NGF-stimulated retrograde transport of trkA in the mammalian nervous system[J].J Cell Biol,1995,130(1):149-156.
[35]ZHOU S,CHEN L S,MIYAUCHI Y,et al.Mechanisms of cardiac nerve sprouting after myocardial infarction in dogs[J].Circ Res,2004,95(1):76-83.
[36]BANDTLOW C,DECHANT G.From cell death to neuronal regeneration,effects of the p75 neurotrophin receptor depend on interactions with partner subunits[J].Sci STKE,2004,2004(235):pe24.
[37]KAPLAN D R,MILLER F D.Axon growth inhibition:signals from the p75 neurotrophin receptor[J].Nat Neurosci,2003,6(5):435-436.
[38]LORENTZ C U,ALSTON E N,BELCIK T,et al.Heterogeneous ventricular sympathetic innervation,altered beta-adrenergic receptor expression,and rhythm instability in mice lacking the p75 neurotrophin receptor[J].Am J Physiol Heart Circ Physiol,2010,298(6):H1652-H1660.
[39]ZHOU S,CAO J M,TEBB Z D,et al.Modulation of QT interval by cardiac sympathetic nerve sprouting and the mechanisms of ventricular arrhythmia in a canine model of sudden cardiac death[J].J Cardiovasc Electrophysiol,2001,12(9):1068-1073.
[40]TSAI J,CAO J M,ZHOU S,et al.T wave alternans as a predictor of spontaneous ventricular tachycardia in a canine model of sudden cardiac death[J].J Cardiovasc Electrophysiol,2002,13(1):51-55.
[41]CAO J M,QU Z,KIM Y H,et al.Spatiotemporal heterogeneity in the induction of ventricular fibrillation by rapid pacing:importance of cardiac restitution properties[J].Circ Res,1999,84(11):1318-1331.
[42]JANSE M J.Electrophysiological changes in heart failure and their relationship to arrhythmogenesis[J].Cardiovasc Res,2004,61(2):208-217.
[43]NERBONNE J M.Molecular basis of functional voltage-gated K+channel diversity in the mammalian myocardium[J].J Physiol,2000,525(Pt 2):285-298.
[44]KASSIRI Z,HAJJAR R,BACKX P H.Molecular components of transient outward potassium current in cultured neonatal rat ventricular myocytes[J].JMol Med(Berl),2002,80(6):351-358.
[45]DHAMOON A S,PANDIT S V,SARMAST F,et al.Unique Kir2.x properties determine regional and species differences in the cardiac inward rectifier K+current[J].Circ Res,2004,94(10):1332-1339.
[46]REN C,WANG F,LI G,et al.Nerve sprouting suppresses myocardial Itoand IK1channels and increases severity to ventricular fibrillation in rat[J]Auton Neurosci,2008,144(1-2):22-29.
[47]BOSCH R F,SCHNECK A C,KIEHN J,et al Beta3-Adrenergic regulation of an ion channel in the heart-inhibition of the slow delayed rectifier potassium current IKsin guinea pig ventricular myocytes[J].Cardiovasc Res,2002,56(3):393-403.
[48]GILL S S,PULIDO O M.Glutamate receptors in peripheral tissues:current knowledge,future research,and implications for toxicology[J].Toxicol Pathol,2001,29(2):208-223.
[49]LüJ,GAO X,GU J,et al.Nerve sprouting contributes to increased severity of ventricular tachyarrhythmias by upregulating iGluRs in rats with healed myocardial necrotic injury[J].J Mol Neurosci,2012,48(2):448-455.
[50]GAO X,XU X,PANG J,et al.NMDA receptor activation induces mitochondrial dysfunction,oxidative stress and apoptosis in cultured neonatal rat cardiomyocytes[J].Physiol Res,2007,56(5):559-569.
[51]PACIFICO A,HENRY P D.Structural pathways and prevention of heart failure and sudden death[J]J Cardiovasc Electrophysiol,2003,14(7):764-775.
[52]KALIN A,USHER-SMITH J,JONES V J,et al Cardiac arrhythmia:a simple conceptual framework[J]Trends Cardiovasc Med,2010,20(3):103-107.
[53]YU T S,WANG X,ZHANG H D,et al.Evaluation of specific neural marker GAP-43 and THcombined with Masson-trichrome staining for forensic autopsy cases with old myocardial infarction[J]Int J Legal Med,2018,132(1):187-195.
[2]LUO D,HU H,QIN Z,et al.Stimulation of ganglionated plexus attenuates cardiac neural remodeling and heart failure progression in a canine model of acute heart failure post-myocardial infarction[J].Auton Neurosci,2017,208:73-79.
[3]D’ELIA E,PASCALE A,MARCHESI N,et al.Novel approaches to the post-myocardial infarction/heart failure neural remodeling[J].Heart Fail Rev,2014,19(5):611-619.
[4]CAO J M,FISHBEIN M C,HAN J B,et al.Relationship between regional cardiac hyperinnervation and ventricular arrhythmia[J].Circulation,2000,101(16):1960-1969.
[5]CAO J M,CHEN L S,KENKNIGHT B H,et al.Nerve sprouting and sudden cardiac death[J].Circ Res,2000,86(7):816-821.
[6]WANG Y,XUAN Y L,HU H S,et al.Risk of ventricular arrhythmias after myocardial infarction with diabetes associated with sympathetic neural remodeling in rabbits[J].Cardiology,2012,121(1):1-9.
[7]CHEN P S,CHEN L S,CAO J M,et al.Sympathetic nerve sprouting,electrical remodeling and the mechanisms of sudden cardiac death[J].Cardiovasc Res,2001,50(2):409-416.
[8]GUYENET P G.The sympathetic control of blood pressure[J].Nat Rev Neurosci,2006,7(5):335-346.
[9]TAN A Y,VERRIER R L.The role of the autonomic nervous system in cardiac arrhythmias[J].Handb Clin Neurol,2013,117:135-145.
[10]VRACKO R,THORNING D,FREDERICKSON RG.Fate of nerve fibers in necrotic,healing,and healed rat myocardium[J].Lab Invest,1990,63(4):490-501.
[11]NORI S L,GAUDINO M,ALESSANDRINI F,et al.Immunohistochemical evidence for sympathetic denervation and reinnervation after necrotic injury in rat myocardium[J].Cell Mol Biol(Noisy-le-grand),1995,41(6):799-807.
[12]FALLEN E L,COATES G,NAHMIAS C,et al.Recovery rates of regional sympathetic reinnervation and myocardial blood flow after acute myocardial infarction[J].Am Heart J,1999,137(5):863-869.
[13]CHEN Z L,YU W M,STRICKLAND S.Peripheral regeneration[J].Annu Rev Neurosci,2007,30:209-233.
[14]JESSEN K R,MIRSKY R.Negative regulation of myelination:relevance for development,injury,and demyelinating disease[J].Glia,2008,56(14):1552-1565.
[15]FONTANA X,HRISTOVA M,DA COSTA C,et al.c-Jun in Schwann cells promotes axonal regeneration and motoneuron survival via paracrine signaling[J].J Cell Biol,2012,198(1):127-141.
[16]BRUSHART T M,ASPALTER M,GRIFFIN J W,et al.Schwann cell phenotype is regulated by axon modality and central-peripheral location,and persists in vitro[J].Exp Neurol,2013,247:272-281.
[17]WOOD M D,MACKINNON S E.Pathways regulating modality-specific axonal regeneration in peripheral nerve[J].Exp Neurol,2015,265:171-175.
[18]SCHEIB J,H?KE A.Advances in peripheral nerve regeneration[J].Nat Rev Neurol,2013,9(12):668-676.
[19]MARTINI R,FISCHER S,LóPEZ-VALES R,et al.Interactions between Schwann cells and macrophages in injury and inherited demyelinating disease[J].Glia,2008,56(14):1566-1577.
[20]ROTSHENKER S.Wallerian degeneration:the innate-immune response to traumatic nerve injury[J].J Neuroinflammation,2011,8:109.
[21]CAFFERTY W B,GARDINER N J,GAVAZZI I,et al.Leukemia inhibitory factor determines the growth status of injured adult sensory neurons[J].J Neurosci,2001,21(18):7161-7170.
[22]BAUER S,KERR B J,PATTERSON P H.The neuropoietic cytokine family in development,plasticity,disease and injury[J].Nat Rev Neurosci,2007,8(3):221-232.
[23]BARRETTE B,HéBERT M A,FILALI M,et al.Requirement of myeloid cells for axon regeneration[J].J Neurosci,2008,28(38):9363-9376.
[24]NIEMI J P,DEFRANCESCO-LISOWITZ A,ROLDáN-HERNáNDEZ L,et al.A critical role for macrophages near axotomized neuronal cell bodies in stimulating nerve regeneration[J].J Neurosci,2013,33(41):16236-16248.
[25]CATTIN A L,BURDEN J J,van EMMENISL,et al.Macrophage-induced blood vessels guide Schwann cell-mediated regeneration of peripheral nerves[J].Cell,2015,162(5):1127-1139.
[26]DUBOVY P,JANCáLEK R,KUBEK T.Role of inflammation and cytokines in peripheral nerve regeneration[J].Int Rev Neurobiol,2013,108:173-206.
[27]EMANUELE E,POLITI P,BIANCHI M,et al.Raised plasma nerve growth factor levels associated with early-stage romantic love[J].Psychoneuroendocrinology,2006,31(3):288-294.
[28]MIAS C,COATRIEUX C,DENIS C,et al.Cardiac fibroblasts regulate sympathetic nerve sprouting and neurocardiac synapse stability[J].PLoS One,2013,8(11):e79068.
[29]WERNLI G,HASAN W,BHATTACHERJEE A,et al.Macrophage depletion suppresses sympathetic hyperinnervation following myocardial infarction[J].Basic Res Cardiol,2009,104(6):681-693.
[30]ZHANG H,YUAN X,JIN P F,et al.Alteration of parasympathetic/sympathetic ratio in the infarcted myocardium after Schwann cell transplantation modified electrophysiological function of heart:a novel antiarrhythmic therapy[J].Circulation,2010,122(S11):S193-S200.
[31]ZHOU L,TOO H P.Mitochondrial localized STAT3is involved in NGF induced neurite outgrowth[J].PLoS One,2011,6(6):e21680.
[32]PELLEGRINO M J,HABECKER B A.STAT3 integrates cytokine and neurotrophin signals to promote sympathetic axon regeneration[J].Mol Cell Neurosci,2013,56:272-282.
[33]BEN-YAAKOV K,DAGAN S Y,SEGAL-RUDERY,et al.Axonal transcription factors signal retrogradely in lesioned peripheral nerve[J].Embo J,2012,31(6):1350-1363.
[34]EHLERS M D,KAPLAN D R,PRICE D L,et al.NGF-stimulated retrograde transport of trkA in the mammalian nervous system[J].J Cell Biol,1995,130(1):149-156.
[35]ZHOU S,CHEN L S,MIYAUCHI Y,et al.Mechanisms of cardiac nerve sprouting after myocardial infarction in dogs[J].Circ Res,2004,95(1):76-83.
[36]BANDTLOW C,DECHANT G.From cell death to neuronal regeneration,effects of the p75 neurotrophin receptor depend on interactions with partner subunits[J].Sci STKE,2004,2004(235):pe24.
[37]KAPLAN D R,MILLER F D.Axon growth inhibition:signals from the p75 neurotrophin receptor[J].Nat Neurosci,2003,6(5):435-436.
[38]LORENTZ C U,ALSTON E N,BELCIK T,et al.Heterogeneous ventricular sympathetic innervation,altered beta-adrenergic receptor expression,and rhythm instability in mice lacking the p75 neurotrophin receptor[J].Am J Physiol Heart Circ Physiol,2010,298(6):H1652-H1660.
[39]ZHOU S,CAO J M,TEBB Z D,et al.Modulation of QT interval by cardiac sympathetic nerve sprouting and the mechanisms of ventricular arrhythmia in a canine model of sudden cardiac death[J].J Cardiovasc Electrophysiol,2001,12(9):1068-1073.
[40]TSAI J,CAO J M,ZHOU S,et al.T wave alternans as a predictor of spontaneous ventricular tachycardia in a canine model of sudden cardiac death[J].J Cardiovasc Electrophysiol,2002,13(1):51-55.
[41]CAO J M,QU Z,KIM Y H,et al.Spatiotemporal heterogeneity in the induction of ventricular fibrillation by rapid pacing:importance of cardiac restitution properties[J].Circ Res,1999,84(11):1318-1331.
[42]JANSE M J.Electrophysiological changes in heart failure and their relationship to arrhythmogenesis[J].Cardiovasc Res,2004,61(2):208-217.
[43]NERBONNE J M.Molecular basis of functional voltage-gated K+channel diversity in the mammalian myocardium[J].J Physiol,2000,525(Pt 2):285-298.
[44]KASSIRI Z,HAJJAR R,BACKX P H.Molecular components of transient outward potassium current in cultured neonatal rat ventricular myocytes[J].JMol Med(Berl),2002,80(6):351-358.
[45]DHAMOON A S,PANDIT S V,SARMAST F,et al.Unique Kir2.x properties determine regional and species differences in the cardiac inward rectifier K+current[J].Circ Res,2004,94(10):1332-1339.
[46]REN C,WANG F,LI G,et al.Nerve sprouting suppresses myocardial Itoand IK1channels and increases severity to ventricular fibrillation in rat[J]Auton Neurosci,2008,144(1-2):22-29.
[47]BOSCH R F,SCHNECK A C,KIEHN J,et al Beta3-Adrenergic regulation of an ion channel in the heart-inhibition of the slow delayed rectifier potassium current IKsin guinea pig ventricular myocytes[J].Cardiovasc Res,2002,56(3):393-403.
[48]GILL S S,PULIDO O M.Glutamate receptors in peripheral tissues:current knowledge,future research,and implications for toxicology[J].Toxicol Pathol,2001,29(2):208-223.
[49]LüJ,GAO X,GU J,et al.Nerve sprouting contributes to increased severity of ventricular tachyarrhythmias by upregulating iGluRs in rats with healed myocardial necrotic injury[J].J Mol Neurosci,2012,48(2):448-455.
[50]GAO X,XU X,PANG J,et al.NMDA receptor activation induces mitochondrial dysfunction,oxidative stress and apoptosis in cultured neonatal rat cardiomyocytes[J].Physiol Res,2007,56(5):559-569.
[51]PACIFICO A,HENRY P D.Structural pathways and prevention of heart failure and sudden death[J]J Cardiovasc Electrophysiol,2003,14(7):764-775.
[52]KALIN A,USHER-SMITH J,JONES V J,et al Cardiac arrhythmia:a simple conceptual framework[J]Trends Cardiovasc Med,2010,20(3):103-107.
[53]YU T S,WANG X,ZHANG H D,et al.Evaluation of specific neural marker GAP-43 and THcombined with Masson-trichrome staining for forensic autopsy cases with old myocardial infarction[J]Int J Legal Med,2018,132(1):187-195.