Urocortin介导的对心脏保护作用的调节及针灸效应的研究分析
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摘要
在心肌缺血损伤过程中,心脏保护因子Urocortin(Ucn)可以通过cAMP/PKA、PI3K-Akt、CaMKII、NO-cGMP、MAPK等多条信号通路进行干预,而在这个过程中介入针灸疗法同样可以通过这些途径对心肌进行保护,而且多条信号通路可以相互影响,机制非常复杂。就Ucn与针灸对缺血心肌在信号通路方面的保护机制进行归纳总结分析,以期为进一步探讨针灸对心脏保护的机制研究以及临床应用提供更广阔的思路。
In the process of myocardial ischemial injury, Urocortin(Ucn), known as heart protective factor, plays
In the process of myocardial ischemial injury, Urocortin(Ucn), known as heart protective factor, plays
引文
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[3] Vaughan J, Donaldson C, Bittencourt J, et al. Urocotin,a mammalian neuropeptide related to fish urotensin and to corticotrophin-realeasing factor[J]. Nature, 1995,378(6554):287-292.
[4] Chen J,Ren Y,Tang Y,et al.Acupuncture therapy for angina pectoris: a systematic review[J]. J Tradit Chin Med 2012,32(4):494-501.
[5] 王睿,庄艺.针刺改善心肌缺血中枢神经效应机制的研究进展[J].国际中医中药杂志,2017,39(5):472-474.
[6] 何苏云,卢圣锋,朱冰梅.针灸抗心肌缺血机制研究及其表观遗传调控机制研究探讨[J].针刺研究,2014,39(1):73-78.
[7] 肖燕,丁亮,顾一煌.针灸对心肌缺血再灌注损伤细胞凋亡信号转到通路影响的研究进展[J].针刺研究,2017,42(5):463-466.
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[9] Minguet S,Huber M,Rosenkranz L,et al.Adenosinc and cAMP are potent inhibitors of the NF-kappa B pathway downsteam of immunoreceptors[J].European journal of immunology,2005,35(1):31-41.
[10] Sanada S,KinakazeM,Papst PJ,et al.Cardioprotective effect afforded by transient exposure to phosphodiesterase Ⅲ inhibitors:the role of protein kinase A and p38 mintogen-activated protein kinase[J].Circulation,2001,104(6):705-710.
[11] Markovic D, Punn A, Lehnert H, et al. Molecular determinants and feedback circuits regulating type 2 CRH receptor signal integration[J]. BiochimBiophysActa, 2011,1813(5), 896-907.
[12] 张志雄,包怡敏,郁礼兴,等.迷走神经在电针提高急性心肌缺血早期室颤阈中的作用[J].上海针灸,2000,19(5):36-38.
[13] 王颖,李迪,戴俭宇,等.电针内关穴及列缺穴对心肌缺血大鼠心肌细胞蛋白激酶表达的影响[J].中国中西医结合杂志,2015,35(3):338-342.
[14] Van Rooij E,Deovendans PA,De Theije CC,et al.Requirement of nuclear factor of activated T-cells in calcineurin-mediated cardiomyocyte hypertrophy[J].J Biol Chem,2002,277(50):48617-48626.
[15] Osaki M,Oshimura M,Ito H.PI3K-Akt pathway:its functions and alterations in human cancer [J].Apoptosis,2004,9(6):667-676.
[16] Deng C,Sun Z,Tong G,et al.α-Lipoic acid reduces infarct size and preserves cardic preserves cardic function in rat myocardial ischemia/reperfusion injury through activation of PI3K/Akt/Nrf2 pathway[J].PLOS One,2013,8(3): e58371.
[17] Quan W,Wu B,Bai Y,et al.Magnesium lithospermate B improves myocardial function and prevents simulated ischemia/reperfusion injury indued H9c2 cardiomyocytes apoptosis thtoughAkt-dependent pathway[J].J Ethnopharmacol,2014,151(1):714-721.
[18] Rossant CJ,Pinnock RD, Hughes J,et al. Corticotropin-releasing factor type 1 and type 2alpha receptors regulate phosphorylation of calcium/cyclic adenosine 30,50- monophosphate response element-binding protein and activation of p42/p44 mitogen-activated protein kinase[J]. Endocrinology,1999,140(4):1525-1536.
[19] Walther S, Pluteanu F, Renz S. et al. Urocortin 2 stimulates nitric oxide production in ventricular myoctytes via Akt- and PKA-mediated phosphorylation of eNOS at serine 1177[J]. Am J Physiol Heart Circ Physiol, 2014,307(5): H689-H700.
[20] 王华,望庐山,梁凤霞,等.基于PI3K-Akt信号通路探讨标本配穴对慢性心肌缺血大鼠的保护作用及机制[J].中华中医药杂志,2016,31(9):3475-3480.
[21] 王华,望庐山,梁凤霞,等.电针治疗慢性心肌缺血大鼠心电图、心肌病理形态及PI3K-Akt信号通路的影响[J].中国针灸,2016,36(4):389-395.
[22] Yang LZ, Kocksk?mper J, Khan S,et al. cAMP- and Ca2+/calmodulin-dependent protein kinases mediate inotropic, lusitropic and arrhythmogenic effects of urocortin 2 in mouse ventricular myocytes[J]. Br J Pharmacol,2011,162(2), 544-556.
[23] Grossini E,Molinari C, Mary DA, et al. Urocortin II induces nitric oxide production through cAMP and Ca2+ related pathways in endothelial cells[J]. CellPhysiolBiochem,2009,23(1-3):87-96.
[24] Grossini E,Caimmi PP, Molinari C, et al. Modulation of calcium movements by urocortin II in endothelial cells[J]. Cell Physiol Biochem,2010,25(2-3):221-232.
[25] 田岳凤,张斌仁,高海宁,等.针刺对心肌缺血再灌注损伤大鼠心肌阻滞CaMKII表达及细胞凋亡的影响[J].中华中医药杂志,2015,30(8):2983-2986.
[26] 任路,马铁明,刘旭来,等.电针对缺血再灌注损伤家兔心肌肌浆网Ca2+-ATPase活性的影响[J].中医研究,2007,20(8):18-20.
[27] Cury Y, Picolo G, Gutierrez VP, et al. Pain and analgesia: The dual effect of nitric oxide in the nociceptive system[J]. Nitric Oxide, 2011, 25: 243-254.
[28] 兰晓莉,裴著果,张永学.NO-cGMP通路在早期心肌缺血预适应中的作用[J].华中科技大学学报(医学版),2006,35(6):731-733.
[29] Sabino JP, Bombarda G, da Silva CA, et al. Role of the spinal cord NO/cGMP pathway in the control of arterial pressure and heart rate[J]. Pflugers Arch, 2011, 461: 23-28.
[30] Danson EJ, Paterson DJ. Enhanced neuronal nitric oxide synthase expression is central to cardiac vagal phenotype in exercise-trained mice[J]. J Physiol, 2003,546: 225-232.
[31] Cantarella G, Lempereur L, Lombardo G,et al. Divergent effects of corticotropin releasing hormone on endothelial cell nitric oxide synthase are associated with different expression of CRH type 1 and 2 receptors[J]. Br J Pharmacol, 2001,134(4):837-844.
[32] Grossini E, Molinari C, Mary DA, et al. The effect of urocortin II administration on the coronary circulation and cardiac function in the anaesthetized pig is nitric-oxide-dependent[J].EurJ Pharmacol, 2008,578(2-3): 242-248.
[33] 王友京,董晓彤,王双昆,等.电针对急性心肌缺血大鼠血浆中ET、NO和CGRP含量的影响[J].中国中医基础医学杂志,2002,8(6):74-75,80.
[34] 田岳凤,林亚平,严洁,等.电针内关穴对心肌缺血-再灌注损伤预防保护作用的实验研究(I)—对CK、ET、MDA、NO、NOS等的影响[J].中国中西医结合急救杂志,2002,9(1):12-14.
[35] 张志雄,包怡敏,郁礼兴,等.迷走神经在电针提高急性心肌缺血早期室颤阈中的作用[J].上海针灸杂志,2000,19(5):36-38.
[36] Makhlouf GM, Murthy KS.Singal transduction in gastrointestinal smooth muscle[J]. Cell signal,1997,9(3-4):269-276.
[37] Brar BK, Jonassen AK, Stephanou A, et al. Urocortin Protects against Ischemic and Reperfusion Injury via a MAPK-dependent Pathway[J]. J Biol Chem, 2000,275(12):8508-8514.
[38] Gordon JM, Dusting GJ, Woodman OL, et al. Cardioprotective action of CRF peptide urocortin against simulated ischemia in adult rat cardiomyocytes[J]. Am J Physiol Heart CircPhysiol, 2003;284(1):H330-H336.
[39] Lawrence KM, Kabir AM, Bellahcene M, et al. Cardioprotection mediated by urocortin is dependent on PKCεactivation[J]. FASEB J,2005,19(7):831-833.
[40] Nishizuka Y. Protein kinase C and lipid signaling for sustained cellular responses[J]. FASEB J, 1995,9(7):484-496.
[41] Adderley SR, Fizgerald DJ. Oxidative damage of cardiomyocytes is limited by extracellular regulated kinases 1/2-mediated induction of cyclooxygenase-2[J]. J BiolChem, 1999, 274(8): 5038-5046.
[42] Smani T, Calderón-Sanchez E, Gómez-Hurtado N, et al. Mechanisms underlying the activation of L-type calcium channels by urocortin in rat ventricular myocytes[J]. Cardiovascular Res,2010,87(3):459-466.
[43] 蒋璘,何可,陈楚淘,等.电针干预自发性高血压大鼠主动脉丝裂原活化蛋白激酶磷酸酶1及磷酸化细胞外信号调节激酶1/2蛋白的表达[J].中国组织工程研究与临床康复,2010,14(20):3686-3690.
[44] 田岳凤,王荣,李雷勇,等.针刺手厥阴经穴对缺血再灌注损伤心肌细胞蛋白激酶C 表达的影响[J].中医杂志,2007,48(8):713-715.
[45] 胡惠林,翟昌林,唐关敏,等.针灸预处理抑制炎症相关蛋白表达对心肌缺血再灌注损伤的保护作用[J].心电与循环,2017,36(5):321-325.
[46] Huang M, Kempuraj D, Papadopoulou N,et al. Urocortin induces interleukin-6 release from rat cardiomyocytes through p38 MAP kinase, ERK and NF-kappaBactivation[J]. J MolEndocrinol, 2009,42(5):397-405.
[47] 张志雄,包怡敏,郁礼兴,等.迷走神经在电针提高急性心肌缺血早期室颤阈中的作用[J].上海针灸杂志,2000,19(5):36-38.
[48] Brar BK,Jonassen AK, Egorina EM, et al.Urocortin-II and urocortin-III are cardioprotective against ischemia reperfusion injury: an essential endogenous cardioprotective role for corticotropin releasing factor receptor type 2 in the murine heart[J]. Endocrinology,2004,145(1):24-35.
[49] Van KolenK, Dautzenberg FM, Verstraeten K,et al. Corticotropin releasing factor-induced ERK phosphorylation in AtT20 cells occurs via a cAMP-dependent mechanism requiring EPAC2[J]. Neuropharmacology, 2010,58(1): 135-144.
[50] Soria LR,Gradilone SA,Larocca MC,et al.Glucagon induces the gene expression of aquaporin-9 water channels in the rat hepatocyte[J].AM J PhysiolRegulIntegr Comp Physiol,2009,296(4):R1274-1281.
[2] Nishikimi T, Miyata A, Horio T, et al. Urocortin, a member of the corticotropin-releasing factor family, in normal and diseased heart[J]. Am J Physiol Heart Circ Physio.2000,279(6):3031-3039.
[3] Vaughan J, Donaldson C, Bittencourt J, et al. Urocotin,a mammalian neuropeptide related to fish urotensin and to corticotrophin-realeasing factor[J]. Nature, 1995,378(6554):287-292.
[4] Chen J,Ren Y,Tang Y,et al.Acupuncture therapy for angina pectoris: a systematic review[J]. J Tradit Chin Med 2012,32(4):494-501.
[5] 王睿,庄艺.针刺改善心肌缺血中枢神经效应机制的研究进展[J].国际中医中药杂志,2017,39(5):472-474.
[6] 何苏云,卢圣锋,朱冰梅.针灸抗心肌缺血机制研究及其表观遗传调控机制研究探讨[J].针刺研究,2014,39(1):73-78.
[7] 肖燕,丁亮,顾一煌.针灸对心肌缺血再灌注损伤细胞凋亡信号转到通路影响的研究进展[J].针刺研究,2017,42(5):463-466.
[8] Inserte J,Garcia-Dorado D,Ruiz-Meana M,et al.Ischemic preconditioning attenuates calpain-mediated degradation of structural proteins through a protein kinase A-dependent mechanism[J].Cardiovasc Res,2004,64(1):105-114.
[9] Minguet S,Huber M,Rosenkranz L,et al.Adenosinc and cAMP are potent inhibitors of the NF-kappa B pathway downsteam of immunoreceptors[J].European journal of immunology,2005,35(1):31-41.
[10] Sanada S,KinakazeM,Papst PJ,et al.Cardioprotective effect afforded by transient exposure to phosphodiesterase Ⅲ inhibitors:the role of protein kinase A and p38 mintogen-activated protein kinase[J].Circulation,2001,104(6):705-710.
[11] Markovic D, Punn A, Lehnert H, et al. Molecular determinants and feedback circuits regulating type 2 CRH receptor signal integration[J]. BiochimBiophysActa, 2011,1813(5), 896-907.
[12] 张志雄,包怡敏,郁礼兴,等.迷走神经在电针提高急性心肌缺血早期室颤阈中的作用[J].上海针灸,2000,19(5):36-38.
[13] 王颖,李迪,戴俭宇,等.电针内关穴及列缺穴对心肌缺血大鼠心肌细胞蛋白激酶表达的影响[J].中国中西医结合杂志,2015,35(3):338-342.
[14] Van Rooij E,Deovendans PA,De Theije CC,et al.Requirement of nuclear factor of activated T-cells in calcineurin-mediated cardiomyocyte hypertrophy[J].J Biol Chem,2002,277(50):48617-48626.
[15] Osaki M,Oshimura M,Ito H.PI3K-Akt pathway:its functions and alterations in human cancer [J].Apoptosis,2004,9(6):667-676.
[16] Deng C,Sun Z,Tong G,et al.α-Lipoic acid reduces infarct size and preserves cardic preserves cardic function in rat myocardial ischemia/reperfusion injury through activation of PI3K/Akt/Nrf2 pathway[J].PLOS One,2013,8(3): e58371.
[17] Quan W,Wu B,Bai Y,et al.Magnesium lithospermate B improves myocardial function and prevents simulated ischemia/reperfusion injury indued H9c2 cardiomyocytes apoptosis thtoughAkt-dependent pathway[J].J Ethnopharmacol,2014,151(1):714-721.
[18] Rossant CJ,Pinnock RD, Hughes J,et al. Corticotropin-releasing factor type 1 and type 2alpha receptors regulate phosphorylation of calcium/cyclic adenosine 30,50- monophosphate response element-binding protein and activation of p42/p44 mitogen-activated protein kinase[J]. Endocrinology,1999,140(4):1525-1536.
[19] Walther S, Pluteanu F, Renz S. et al. Urocortin 2 stimulates nitric oxide production in ventricular myoctytes via Akt- and PKA-mediated phosphorylation of eNOS at serine 1177[J]. Am J Physiol Heart Circ Physiol, 2014,307(5): H689-H700.
[20] 王华,望庐山,梁凤霞,等.基于PI3K-Akt信号通路探讨标本配穴对慢性心肌缺血大鼠的保护作用及机制[J].中华中医药杂志,2016,31(9):3475-3480.
[21] 王华,望庐山,梁凤霞,等.电针治疗慢性心肌缺血大鼠心电图、心肌病理形态及PI3K-Akt信号通路的影响[J].中国针灸,2016,36(4):389-395.
[22] Yang LZ, Kocksk?mper J, Khan S,et al. cAMP- and Ca2+/calmodulin-dependent protein kinases mediate inotropic, lusitropic and arrhythmogenic effects of urocortin 2 in mouse ventricular myocytes[J]. Br J Pharmacol,2011,162(2), 544-556.
[23] Grossini E,Molinari C, Mary DA, et al. Urocortin II induces nitric oxide production through cAMP and Ca2+ related pathways in endothelial cells[J]. CellPhysiolBiochem,2009,23(1-3):87-96.
[24] Grossini E,Caimmi PP, Molinari C, et al. Modulation of calcium movements by urocortin II in endothelial cells[J]. Cell Physiol Biochem,2010,25(2-3):221-232.
[25] 田岳凤,张斌仁,高海宁,等.针刺对心肌缺血再灌注损伤大鼠心肌阻滞CaMKII表达及细胞凋亡的影响[J].中华中医药杂志,2015,30(8):2983-2986.
[26] 任路,马铁明,刘旭来,等.电针对缺血再灌注损伤家兔心肌肌浆网Ca2+-ATPase活性的影响[J].中医研究,2007,20(8):18-20.
[27] Cury Y, Picolo G, Gutierrez VP, et al. Pain and analgesia: The dual effect of nitric oxide in the nociceptive system[J]. Nitric Oxide, 2011, 25: 243-254.
[28] 兰晓莉,裴著果,张永学.NO-cGMP通路在早期心肌缺血预适应中的作用[J].华中科技大学学报(医学版),2006,35(6):731-733.
[29] Sabino JP, Bombarda G, da Silva CA, et al. Role of the spinal cord NO/cGMP pathway in the control of arterial pressure and heart rate[J]. Pflugers Arch, 2011, 461: 23-28.
[30] Danson EJ, Paterson DJ. Enhanced neuronal nitric oxide synthase expression is central to cardiac vagal phenotype in exercise-trained mice[J]. J Physiol, 2003,546: 225-232.
[31] Cantarella G, Lempereur L, Lombardo G,et al. Divergent effects of corticotropin releasing hormone on endothelial cell nitric oxide synthase are associated with different expression of CRH type 1 and 2 receptors[J]. Br J Pharmacol, 2001,134(4):837-844.
[32] Grossini E, Molinari C, Mary DA, et al. The effect of urocortin II administration on the coronary circulation and cardiac function in the anaesthetized pig is nitric-oxide-dependent[J].EurJ Pharmacol, 2008,578(2-3): 242-248.
[33] 王友京,董晓彤,王双昆,等.电针对急性心肌缺血大鼠血浆中ET、NO和CGRP含量的影响[J].中国中医基础医学杂志,2002,8(6):74-75,80.
[34] 田岳凤,林亚平,严洁,等.电针内关穴对心肌缺血-再灌注损伤预防保护作用的实验研究(I)—对CK、ET、MDA、NO、NOS等的影响[J].中国中西医结合急救杂志,2002,9(1):12-14.
[35] 张志雄,包怡敏,郁礼兴,等.迷走神经在电针提高急性心肌缺血早期室颤阈中的作用[J].上海针灸杂志,2000,19(5):36-38.
[36] Makhlouf GM, Murthy KS.Singal transduction in gastrointestinal smooth muscle[J]. Cell signal,1997,9(3-4):269-276.
[37] Brar BK, Jonassen AK, Stephanou A, et al. Urocortin Protects against Ischemic and Reperfusion Injury via a MAPK-dependent Pathway[J]. J Biol Chem, 2000,275(12):8508-8514.
[38] Gordon JM, Dusting GJ, Woodman OL, et al. Cardioprotective action of CRF peptide urocortin against simulated ischemia in adult rat cardiomyocytes[J]. Am J Physiol Heart CircPhysiol, 2003;284(1):H330-H336.
[39] Lawrence KM, Kabir AM, Bellahcene M, et al. Cardioprotection mediated by urocortin is dependent on PKCεactivation[J]. FASEB J,2005,19(7):831-833.
[40] Nishizuka Y. Protein kinase C and lipid signaling for sustained cellular responses[J]. FASEB J, 1995,9(7):484-496.
[41] Adderley SR, Fizgerald DJ. Oxidative damage of cardiomyocytes is limited by extracellular regulated kinases 1/2-mediated induction of cyclooxygenase-2[J]. J BiolChem, 1999, 274(8): 5038-5046.
[42] Smani T, Calderón-Sanchez E, Gómez-Hurtado N, et al. Mechanisms underlying the activation of L-type calcium channels by urocortin in rat ventricular myocytes[J]. Cardiovascular Res,2010,87(3):459-466.
[43] 蒋璘,何可,陈楚淘,等.电针干预自发性高血压大鼠主动脉丝裂原活化蛋白激酶磷酸酶1及磷酸化细胞外信号调节激酶1/2蛋白的表达[J].中国组织工程研究与临床康复,2010,14(20):3686-3690.
[44] 田岳凤,王荣,李雷勇,等.针刺手厥阴经穴对缺血再灌注损伤心肌细胞蛋白激酶C 表达的影响[J].中医杂志,2007,48(8):713-715.
[45] 胡惠林,翟昌林,唐关敏,等.针灸预处理抑制炎症相关蛋白表达对心肌缺血再灌注损伤的保护作用[J].心电与循环,2017,36(5):321-325.
[46] Huang M, Kempuraj D, Papadopoulou N,et al. Urocortin induces interleukin-6 release from rat cardiomyocytes through p38 MAP kinase, ERK and NF-kappaBactivation[J]. J MolEndocrinol, 2009,42(5):397-405.
[47] 张志雄,包怡敏,郁礼兴,等.迷走神经在电针提高急性心肌缺血早期室颤阈中的作用[J].上海针灸杂志,2000,19(5):36-38.
[48] Brar BK,Jonassen AK, Egorina EM, et al.Urocortin-II and urocortin-III are cardioprotective against ischemia reperfusion injury: an essential endogenous cardioprotective role for corticotropin releasing factor receptor type 2 in the murine heart[J]. Endocrinology,2004,145(1):24-35.
[49] Van KolenK, Dautzenberg FM, Verstraeten K,et al. Corticotropin releasing factor-induced ERK phosphorylation in AtT20 cells occurs via a cAMP-dependent mechanism requiring EPAC2[J]. Neuropharmacology, 2010,58(1): 135-144.
[50] Soria LR,Gradilone SA,Larocca MC,et al.Glucagon induces the gene expression of aquaporin-9 water channels in the rat hepatocyte[J].AM J PhysiolRegulIntegr Comp Physiol,2009,296(4):R1274-1281.