有氧运动通过鸢尾素改善慢性心力衰竭的机制
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摘要
背景:慢性心力衰竭与心肌线粒体稳态异常以及心肌能量代谢紊乱等密切相关。解偶联蛋白2是位于线粒体内膜上的质子泵,与心肌的氧化应激、能量代谢和细胞凋亡关系密切,在慢性心力衰竭病理生理过程中起着极其重要作用。目的:总结鸢尾素对慢性心力衰竭的影响,讨论有氧运动通过鸢尾素改善慢性心力衰竭的机制。方法:应用计算机检索PubMed和CNKI等数据库从2001年至2018年收录的与鸢尾素和慢性心力衰竭相关的文献。英文检索词为:"aerobic exercise","Irisin","chronic heart failure",中文检索词为:"有氧运动","鸢尾素","慢性心力衰竭"。排除无关和重复文献,最后纳入53篇文章进行分析总结,包括8篇中文和45篇英文文献。结果与结论:鸢尾素可抑制活性氧生成,可以模拟有氧运动带来的良好效益,在有氧运动改善慢性心力衰竭中起着重要的作用,因此鸢尾素可作为运动治疗心力衰竭的潜在靶点。长期的有氧运动可能通过鸢尾素/活性氧/解耦联蛋白2途径改善心力衰竭过程。
BACKGROUND: Chronic heart failure is closely related to the homeostasis of myocardial mitochondria and disorders of myocardial energy metabolism. As a proton pump on the membrane of mitochondria, uncoupling protein 2 is closely related to myocardial oxidative stress, energy metabolism and cardiomyocyte apoptosis. It plays an extremely important part in the pathophysiological process of myocardium.OBJECTIVE: To review the effects of irisin on chronic heart failure and explore the mechanism of aerobic exercise improving chronic heart failure by irisin. METHODS: A computer-based retrieval of PubMed and CNKI databases was performed to search relevant articles concerning irisin and chronic heart failure published from 2001 to 2018, using the keywords "aerobic exercise, irisin, chronic heart failure" in English and Chinese, respectively. After removal of repetitive and irrelevant articles, 53 eligible articles were finally reviewed, including 45 English and 8 Chinese articles. RESULTS AND CONCLUSION: Irisin may inhibit the production of reactive oxygen species and simulate the good benefits of aerobic exercise. Irisin plays an important role in aerobic exercise improving chronic heart failure and serves as a potential target for exercise therapy for heart failure. Long-term aerobic exercise may improve heart failure through the irisin/reactive oxygen species/uncoupling protein 2 pathway.
BACKGROUND: Chronic heart failure is closely related to the homeostasis of myocardial mitochondria and disorders of myocardial energy metabolism. As a proton pump on the membrane of mitochondria, uncoupling protein 2 is closely related to myocardial oxidative stress, energy metabolism and cardiomyocyte apoptosis. It plays an extremely important part in the pathophysiological process of myocardium.OBJECTIVE: To review the effects of irisin on chronic heart failure and explore the mechanism of aerobic exercise improving chronic heart failure by irisin. METHODS: A computer-based retrieval of PubMed and CNKI databases was performed to search relevant articles concerning irisin and chronic heart failure published from 2001 to 2018, using the keywords "aerobic exercise, irisin, chronic heart failure" in English and Chinese, respectively. After removal of repetitive and irrelevant articles, 53 eligible articles were finally reviewed, including 45 English and 8 Chinese articles. RESULTS AND CONCLUSION: Irisin may inhibit the production of reactive oxygen species and simulate the good benefits of aerobic exercise. Irisin plays an important role in aerobic exercise improving chronic heart failure and serves as a potential target for exercise therapy for heart failure. Long-term aerobic exercise may improve heart failure through the irisin/reactive oxygen species/uncoupling protein 2 pathway.
引文
[1]Bayeva M,Gheorghiade M,Ardehali H.Mitochondria as a therapeutic target in heart failure.J Am Coll Cardiol.2013;61(6):599-610.
[2]Matsuo Y,Gleitsmann K,Mangner N,et al.Fibronectin type IIIdomain containing 5 expression in skeletal muscle in chronic heart failure-relevance of inflammatory cytokines.J Cachexia Sarcopeni.2015;6(1):62-72.
[3]Murray AJ,Panagia M,Hauton D,et al.Plasma free fatty acids and peroxisome proliferator-activated receptor in the control of myocardial uncoupling protein levels.Diabetes.2005;54(12):3496-3502.
[4]De Maeyer C,Beckers P,Vrints CJ,et al.Exercise training in chronic heart failure.Ther Adv Chronic Dis.2013;4(3):105-117.
[5]Wisl?ff U,St?ylen A,Loennechen JP,et al.Superior cardiovascular effect of aerobic interval training versus moderate continuous training in heart failure patients:a randomized study.Circulation.2007;115(24):3086-3094.
[6]Tomczak CR,Thompson RB,Paterson I,et al.Effect of acute high-intensity interval exercise on postexercise biventricular function in mild heart failure.J Appl Physiol.2011;110(2):398-406.
[7]程蕾.有氧运动和抗心力衰竭药物联合作用对慢性心力衰竭患者红细胞分布宽度、心功能及运动能力的影响[J].中国体育科技,2013,49(1):52-56,77.
[8]刘涛,张敏,徐栋,等.运动促进慢性心力衰竭大鼠心肌线粒体生物合成与心肌重构[J].中国运动医学杂志,2011,30(3):250-256.
[9]Bostr?m P,Wu J,Jedrychowski M P,et al.A PGC1α-dependent myokine that drives browning of white fat and thermogenesis.Nature.2012;481(7382):463-468.
[10]Chen K,Xu Z,Liu Y,et al.Irisin protects mitochondria function during pulmonary ischemia/reperfusion injury.Sci Transl Med.2017;9(418):1-14.
[11]Sreedhar A,Zhao Y.Uncoupling protein 2 and metabolic diseases.Mitochondrion.2017;34:135-140.
[12]Wallace DC.A mitochondrial bioenergetic etiology of disease.J Clin Invest.2013;123(4):1405-1412.
[13]Handschin C,Spiegelman BM.The role of exercise and PGC1alpha in inflammation and chronic disease.Nature.2008;454(7203):463-469.
[14]Nakahira K,Haspel JA,Rathinam VA,et al.Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3inflammasome.Nat Immunol.2011;12(3):222-230.
[15]Akhmedov AT,Rybin V,Maríngarcía J.Mitochondrial oxidative metabolism and uncoupling proteins in the failing heart.Heart Fail Rev.2015;20(2):227-249.
[16]Wai T,Garcíaprieto J,Baker MJ,et al.Imbalanced OPA1processing and mitochondrial fragmentation cause heart failure in mice.Science.2015;350(6265):1121-1134.
[17]Givvimani S,Pushpakumar S,Veeranki S,et al.Dysregulation of Mfn2 and Drp-1 proteins in heart failure.Can J Physiol Pharmacol.2014;92(7):583-591.
[18]Doenst T,Nguyen TD,Abel ED.Cardiac metabolism in heart failure-implications beyond ATP production.Circ Res.2013;113(6):709-724.
[19]Van BM,Smeets PJ,Gilde AJ,et al.Metabolic remodelling of the failing heart:the cardiac burn-out syndrome?Cardiovasc Res.2004;61(2):218-226.
[20]Bostr?m P,Wu J,Jedrychowski MP,et al.A PGC1-alphadependent myokine that drives brown-fat-like development of white fat and thermogenesis.Nature.2012;481(7382):463-468.
[21]Aydin S,Kuloglu T,Aydin S,et al.A comprehensive immunohistochemical examination of the distribution of the fat-burning protein Irisin in biological tissues.Peptides.2014;61:130-136.
[22]Kuloglu T,Aydin S,Eren MN,et al.Irisin:a potentially candidate marker for myocardial infarction.Peptides.2014;55(5):85-91.
[23]Xie C,Zhang Y,Tran TDN,et al.Irisin controls growth,intracellular ca2+signals,and mitochondrial thermogenesis in cardiomyoblasts.PLoS One.2015;10(8):e0136816.
[24]Aydin S,Kuloglu T,Aydin S,et al.Cardiac,skeletal muscle and serum irisin responses to with or without water exercise in young and old male rats:cardiac muscle produces more Irisin than skeletal muscle.Peptides.2014;52(2):68-73.
[25]Sanchis-Gomar F,Perez-Quilis C.The p38-PGC-1α-Irisin-betatrophin axis:Exploring new pathways in insulin resistance.Adipocyte.2014;3(1):67-68.
[26]莫显刚,冯健,张莉,等.心力衰竭患者循环irisin水平与心功能的相关性研究[J].临床心血管病杂志,2015,31(8):860-863.
[27]王小龙,刘同祥,赵新祥,等.慢性心力衰竭患者体内irisin水平的变化及临床价值的研究[J].中华临床医师杂志(电子版),2015,9(16):2996-3000.
[28]Wang H,Zhao YT,Zhang S,et al.Irisin plays a pivotal role to protect the heart against ischemia and reperfusion injury.JCell Physiol.2017;232(12):3775-3785.
[29]McLeod CJ,Hoyt RF,Sack MN.UCP2:A functional target in delayed preconditioning induced cardioprotection.Cardiovasc J Afr.2004;15(4supp1):S4-S6.
[30]McLeod CJ,Aziz A,Hoyt RF Jr,et al.Uncoupling proteins 2and 3 function in concert to augment tolerance to cardiac ischemia.J Biol Chem.2005;280(39):33470-33476.
[31]Ji XB,Li XR,Ding H,et al.Inhibition of uncoupling protein2attenuates cardiac hypertrophy induced by transverse aortic constriction in mice.Cell Physiol Biochem.2015;36(5):1688-1698.
[32]Arsenijevic D,Onuma H,Pecqueur C,et al.Disruption of the uncoupling protein-2 gene in mice reveals a role in immunity and reactive oxygen species production.Nat Genet.2000;26(4):435-439.
[33]Bouillaud F.UCP2,not a physiologically relevant uncoupler but a glucose sparing switch impacting ROS production and glucose sensing.Biochim Biophys Acta Bioenerg.2009;1787(5):377-383.
[34]Vozza A,Parisi G,De LF,et al.UCP2 transports C4metabolites out of mitochondria,regulating glucose and glutamine oxidation.Proc Natl Acad Sci.2014;111(3):960-965.
[35]Diano S,Horvath TL.Mitochondrial uncoupling protein2(UCP2)in glucose and lipid metabolism.Trends Mol Med.2012;18(1):52-58.
[36]Fan JG,Zheng XY,Tian LY,et al.Dynamic changes of plasma levels of prostacycline and thromboxane A2 and their correlation with the severity of hepatic injury in rats with nonalcoholic fatty liver disease.Chin J Hepatol.2004;12(11):681-683.
[37]纪丽丽,李晓燕.线粒体解偶联蛋白2在心力衰竭及运动心肌损伤中的研究进展[J].中国循证心血管医学杂志,2015,7(4):566-571.
[38]Yang C,Zhao D,Liu G,et al.Atorvastatin Attenuates Metabolic Remodeling in Ischemic Myocardium through the Downregulation of UCP2 Expression.Int J Med Sci.2018;15(5):517-527.
[39]Ramsden DB,Ho PW,Ho JW,et al.Human neuronal uncoupling proteins4 and 5(UCP4 and UCP5):structural properties,regulation,and physiological role in protection against oxidative stress and mitochondrial dysfunction.Brain Behav.2012;2(4):468-478.
[40]Jezek P,Engstova H,Zackova M,et al.Fatty acid cycling mechanism and mitochondrial uncoupling proteins.Biochim Biophys Acta.1998;1365(1-2):319-327.
[41]李楠,王江,高峰,等.心力衰竭大鼠解偶联蛋白2表达及其对线粒体功能的影响[J].岭南心血管病杂志,2009,15(6):474-478.
[42]李楠.调节底物代谢对衰竭心肌代谢重构的干预作用及相关机制研究[D].重庆:第三军医大学,2010.
[43]Chuang YC,Lin TK,Huang HY,et al.Peroxisome proliferator-activated receptors gamma/mitochondrial uncoupling protein 2 signaling protects against seizure-induced neuronal cell death in the hippocampus following experimental status epilepticus.J Neuroinflamm.2012;9(1):184-202.
[44]Fine EJ,Miller A,Quardros EV,et al.Acetoacetate reduces growth and ATP concentration in cancer cell lines which over-express uncoupling protein 2.Cancer Cell Int.2009;9(7):14-25.
[45]Rousset S,Alvesguerra MC,Mozo J,et al.The Biology of Mitochondrial Uncoupling Proteins.Diabetes.2004;53(Suppl1):S130-135.
[46]Bo H,Jiang N,Ma GD,et al.Regulation of mitochondrial uncoupling respiration during exercise in rat heart:Role of reactive oxygen species(ROS)and uncoupling protein 2.Free Radic Biol Med.2008;44(7):1373-1381.
[47]Boss O,Samec S,Desplanches D,et al.Effect of endurance training on mRNA expression of uncoupling protein 1,2,and3 in rat.Faseb J.1998;12(3):335-339.
[48]Zhang Y,Mu Q,Zhou Z,et al.Protective effect of irisin on atherosclerosis via suppressing oxidized low density lipoprotein induced vascular inflammation and endothelial dysfunction.Plos One.2016;11(6):e0158038.
[49]Peng J,Deng X,Huang W,et al.Irisin protects against neuronal injury induced by oxygen-glucose deprivation in part depends on the inhibition of ROS-NLRP3 inflammatory signaling pathway.Mol Immunol.2017;91:185-194.
[50]Erden Y,Tekin S,Sandal S,et al.Effects of central Irisin administration on the uncoupling proteins in rat brain.Neuroscic Lett.2016;618:6-13.
[51]Tekin S,Erden Y,Ozyalin F,et al.The effects of intracerebroventricular infusion of irisin on feeding behaviour in rats.Neurosci Lett.2017;645:25-32.
[52]王震.不同药物干预心、肾缺血再灌注损伤的作用与机制研究[D].重庆:第三军医大学,2015.
[53]Mailloux RJ,Harper ME.Uncoupling proteins and the control of mitochondrial reactive oxygen species production.Free Radical Bio Med.2011;51(6):1106-1115.
[2]Matsuo Y,Gleitsmann K,Mangner N,et al.Fibronectin type IIIdomain containing 5 expression in skeletal muscle in chronic heart failure-relevance of inflammatory cytokines.J Cachexia Sarcopeni.2015;6(1):62-72.
[3]Murray AJ,Panagia M,Hauton D,et al.Plasma free fatty acids and peroxisome proliferator-activated receptor in the control of myocardial uncoupling protein levels.Diabetes.2005;54(12):3496-3502.
[4]De Maeyer C,Beckers P,Vrints CJ,et al.Exercise training in chronic heart failure.Ther Adv Chronic Dis.2013;4(3):105-117.
[5]Wisl?ff U,St?ylen A,Loennechen JP,et al.Superior cardiovascular effect of aerobic interval training versus moderate continuous training in heart failure patients:a randomized study.Circulation.2007;115(24):3086-3094.
[6]Tomczak CR,Thompson RB,Paterson I,et al.Effect of acute high-intensity interval exercise on postexercise biventricular function in mild heart failure.J Appl Physiol.2011;110(2):398-406.
[7]程蕾.有氧运动和抗心力衰竭药物联合作用对慢性心力衰竭患者红细胞分布宽度、心功能及运动能力的影响[J].中国体育科技,2013,49(1):52-56,77.
[8]刘涛,张敏,徐栋,等.运动促进慢性心力衰竭大鼠心肌线粒体生物合成与心肌重构[J].中国运动医学杂志,2011,30(3):250-256.
[9]Bostr?m P,Wu J,Jedrychowski M P,et al.A PGC1α-dependent myokine that drives browning of white fat and thermogenesis.Nature.2012;481(7382):463-468.
[10]Chen K,Xu Z,Liu Y,et al.Irisin protects mitochondria function during pulmonary ischemia/reperfusion injury.Sci Transl Med.2017;9(418):1-14.
[11]Sreedhar A,Zhao Y.Uncoupling protein 2 and metabolic diseases.Mitochondrion.2017;34:135-140.
[12]Wallace DC.A mitochondrial bioenergetic etiology of disease.J Clin Invest.2013;123(4):1405-1412.
[13]Handschin C,Spiegelman BM.The role of exercise and PGC1alpha in inflammation and chronic disease.Nature.2008;454(7203):463-469.
[14]Nakahira K,Haspel JA,Rathinam VA,et al.Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3inflammasome.Nat Immunol.2011;12(3):222-230.
[15]Akhmedov AT,Rybin V,Maríngarcía J.Mitochondrial oxidative metabolism and uncoupling proteins in the failing heart.Heart Fail Rev.2015;20(2):227-249.
[16]Wai T,Garcíaprieto J,Baker MJ,et al.Imbalanced OPA1processing and mitochondrial fragmentation cause heart failure in mice.Science.2015;350(6265):1121-1134.
[17]Givvimani S,Pushpakumar S,Veeranki S,et al.Dysregulation of Mfn2 and Drp-1 proteins in heart failure.Can J Physiol Pharmacol.2014;92(7):583-591.
[18]Doenst T,Nguyen TD,Abel ED.Cardiac metabolism in heart failure-implications beyond ATP production.Circ Res.2013;113(6):709-724.
[19]Van BM,Smeets PJ,Gilde AJ,et al.Metabolic remodelling of the failing heart:the cardiac burn-out syndrome?Cardiovasc Res.2004;61(2):218-226.
[20]Bostr?m P,Wu J,Jedrychowski MP,et al.A PGC1-alphadependent myokine that drives brown-fat-like development of white fat and thermogenesis.Nature.2012;481(7382):463-468.
[21]Aydin S,Kuloglu T,Aydin S,et al.A comprehensive immunohistochemical examination of the distribution of the fat-burning protein Irisin in biological tissues.Peptides.2014;61:130-136.
[22]Kuloglu T,Aydin S,Eren MN,et al.Irisin:a potentially candidate marker for myocardial infarction.Peptides.2014;55(5):85-91.
[23]Xie C,Zhang Y,Tran TDN,et al.Irisin controls growth,intracellular ca2+signals,and mitochondrial thermogenesis in cardiomyoblasts.PLoS One.2015;10(8):e0136816.
[24]Aydin S,Kuloglu T,Aydin S,et al.Cardiac,skeletal muscle and serum irisin responses to with or without water exercise in young and old male rats:cardiac muscle produces more Irisin than skeletal muscle.Peptides.2014;52(2):68-73.
[25]Sanchis-Gomar F,Perez-Quilis C.The p38-PGC-1α-Irisin-betatrophin axis:Exploring new pathways in insulin resistance.Adipocyte.2014;3(1):67-68.
[26]莫显刚,冯健,张莉,等.心力衰竭患者循环irisin水平与心功能的相关性研究[J].临床心血管病杂志,2015,31(8):860-863.
[27]王小龙,刘同祥,赵新祥,等.慢性心力衰竭患者体内irisin水平的变化及临床价值的研究[J].中华临床医师杂志(电子版),2015,9(16):2996-3000.
[28]Wang H,Zhao YT,Zhang S,et al.Irisin plays a pivotal role to protect the heart against ischemia and reperfusion injury.JCell Physiol.2017;232(12):3775-3785.
[29]McLeod CJ,Hoyt RF,Sack MN.UCP2:A functional target in delayed preconditioning induced cardioprotection.Cardiovasc J Afr.2004;15(4supp1):S4-S6.
[30]McLeod CJ,Aziz A,Hoyt RF Jr,et al.Uncoupling proteins 2and 3 function in concert to augment tolerance to cardiac ischemia.J Biol Chem.2005;280(39):33470-33476.
[31]Ji XB,Li XR,Ding H,et al.Inhibition of uncoupling protein2attenuates cardiac hypertrophy induced by transverse aortic constriction in mice.Cell Physiol Biochem.2015;36(5):1688-1698.
[32]Arsenijevic D,Onuma H,Pecqueur C,et al.Disruption of the uncoupling protein-2 gene in mice reveals a role in immunity and reactive oxygen species production.Nat Genet.2000;26(4):435-439.
[33]Bouillaud F.UCP2,not a physiologically relevant uncoupler but a glucose sparing switch impacting ROS production and glucose sensing.Biochim Biophys Acta Bioenerg.2009;1787(5):377-383.
[34]Vozza A,Parisi G,De LF,et al.UCP2 transports C4metabolites out of mitochondria,regulating glucose and glutamine oxidation.Proc Natl Acad Sci.2014;111(3):960-965.
[35]Diano S,Horvath TL.Mitochondrial uncoupling protein2(UCP2)in glucose and lipid metabolism.Trends Mol Med.2012;18(1):52-58.
[36]Fan JG,Zheng XY,Tian LY,et al.Dynamic changes of plasma levels of prostacycline and thromboxane A2 and their correlation with the severity of hepatic injury in rats with nonalcoholic fatty liver disease.Chin J Hepatol.2004;12(11):681-683.
[37]纪丽丽,李晓燕.线粒体解偶联蛋白2在心力衰竭及运动心肌损伤中的研究进展[J].中国循证心血管医学杂志,2015,7(4):566-571.
[38]Yang C,Zhao D,Liu G,et al.Atorvastatin Attenuates Metabolic Remodeling in Ischemic Myocardium through the Downregulation of UCP2 Expression.Int J Med Sci.2018;15(5):517-527.
[39]Ramsden DB,Ho PW,Ho JW,et al.Human neuronal uncoupling proteins4 and 5(UCP4 and UCP5):structural properties,regulation,and physiological role in protection against oxidative stress and mitochondrial dysfunction.Brain Behav.2012;2(4):468-478.
[40]Jezek P,Engstova H,Zackova M,et al.Fatty acid cycling mechanism and mitochondrial uncoupling proteins.Biochim Biophys Acta.1998;1365(1-2):319-327.
[41]李楠,王江,高峰,等.心力衰竭大鼠解偶联蛋白2表达及其对线粒体功能的影响[J].岭南心血管病杂志,2009,15(6):474-478.
[42]李楠.调节底物代谢对衰竭心肌代谢重构的干预作用及相关机制研究[D].重庆:第三军医大学,2010.
[43]Chuang YC,Lin TK,Huang HY,et al.Peroxisome proliferator-activated receptors gamma/mitochondrial uncoupling protein 2 signaling protects against seizure-induced neuronal cell death in the hippocampus following experimental status epilepticus.J Neuroinflamm.2012;9(1):184-202.
[44]Fine EJ,Miller A,Quardros EV,et al.Acetoacetate reduces growth and ATP concentration in cancer cell lines which over-express uncoupling protein 2.Cancer Cell Int.2009;9(7):14-25.
[45]Rousset S,Alvesguerra MC,Mozo J,et al.The Biology of Mitochondrial Uncoupling Proteins.Diabetes.2004;53(Suppl1):S130-135.
[46]Bo H,Jiang N,Ma GD,et al.Regulation of mitochondrial uncoupling respiration during exercise in rat heart:Role of reactive oxygen species(ROS)and uncoupling protein 2.Free Radic Biol Med.2008;44(7):1373-1381.
[47]Boss O,Samec S,Desplanches D,et al.Effect of endurance training on mRNA expression of uncoupling protein 1,2,and3 in rat.Faseb J.1998;12(3):335-339.
[48]Zhang Y,Mu Q,Zhou Z,et al.Protective effect of irisin on atherosclerosis via suppressing oxidized low density lipoprotein induced vascular inflammation and endothelial dysfunction.Plos One.2016;11(6):e0158038.
[49]Peng J,Deng X,Huang W,et al.Irisin protects against neuronal injury induced by oxygen-glucose deprivation in part depends on the inhibition of ROS-NLRP3 inflammatory signaling pathway.Mol Immunol.2017;91:185-194.
[50]Erden Y,Tekin S,Sandal S,et al.Effects of central Irisin administration on the uncoupling proteins in rat brain.Neuroscic Lett.2016;618:6-13.
[51]Tekin S,Erden Y,Ozyalin F,et al.The effects of intracerebroventricular infusion of irisin on feeding behaviour in rats.Neurosci Lett.2017;645:25-32.
[52]王震.不同药物干预心、肾缺血再灌注损伤的作用与机制研究[D].重庆:第三军医大学,2015.
[53]Mailloux RJ,Harper ME.Uncoupling proteins and the control of mitochondrial reactive oxygen species production.Free Radical Bio Med.2011;51(6):1106-1115.