心肌缺血糖酵解途径中AMPK的分子调控机制以及中医药研究进展
|
摘要
心肌缺血主要指心脏冠脉血流量减少,供氧能力减弱,心肌能量代谢紊乱,导致心脏泵血功能异常的临床病变。心脏是一个高耗氧、高耗能、高代谢率的器官,需要大量的能量来维持其正常的生理功能以及代谢需要。正常情况下70%～90%能量供应主要来源为脂肪酸氧化。但缺血缺氧情况下,心脏通过糖酵解产生少量的ATP给缺氧的心肌细胞补偿供能,以减轻缺血的心肌细胞进一步损伤。最新研究表明,在心肌缺血时,AMP依赖的蛋白激酶(AMPK)的活化是一种适应性应激反应。活化的AMPK可有效抑制心肌坏死和和收缩功能障碍,是治疗心肌梗死、保护损伤心肌的新策略。文章针对心肌缺血糖酵解途径的变化和AMPK在心肌缺血的分子调控机制以及中西医结合药物相关的研究进展进行综述,以期对心肌缺血的分子机制及中西医结合预防治疗心肌缺血提供新的药物靶点与干预环节。
Myocardial ischemia mainly refers to reduced cardiac blood flow, reduced oxygen supply capacity,myocardial metabolic disorders which can lead to abnormal cardiac pump dysfunction. The heart is an organ of high oxygen consumption, high energy consumption, high metabolic rate, it requires a lot of energy to maintain its normal physiological function as well as metabolic needs. Under normal circumstances, 70%～90% of the energy supply is provided by fatty acid oxidation, however, during ischemia and hypoxia condition, the heart gets compensational energy through the glycolysis for hypoxic cardiomyocytes, which can finally protect the ischemic myocardial cells from further damage. Recent studies have shown that activation of AMPK is an adaptive stress response in myocardial ischemia. Activated AMPK can effectively inhibit myocardial necrosis and systolic dysfunction, and provides a new strategy for treatment of myocardial infarction and protection of damaged myocardium. Current study summarizes the patterns of glycolytic pathway and the potential molecular mechanism of AMPK in myocardial ischemia together with the progress of integrated traditional Chinese medicine and western medicine on it.This review can deepen our understanding on molecular mechanism of myocardial ischemia thus to provide new drug targets and interventions for myocardial ischemia.
Myocardial ischemia mainly refers to reduced cardiac blood flow, reduced oxygen supply capacity,myocardial metabolic disorders which can lead to abnormal cardiac pump dysfunction. The heart is an organ of high oxygen consumption, high energy consumption, high metabolic rate, it requires a lot of energy to maintain its normal physiological function as well as metabolic needs. Under normal circumstances, 70%～90% of the energy supply is provided by fatty acid oxidation, however, during ischemia and hypoxia condition, the heart gets compensational energy through the glycolysis for hypoxic cardiomyocytes, which can finally protect the ischemic myocardial cells from further damage. Recent studies have shown that activation of AMPK is an adaptive stress response in myocardial ischemia. Activated AMPK can effectively inhibit myocardial necrosis and systolic dysfunction, and provides a new strategy for treatment of myocardial infarction and protection of damaged myocardium. Current study summarizes the patterns of glycolytic pathway and the potential molecular mechanism of AMPK in myocardial ischemia together with the progress of integrated traditional Chinese medicine and western medicine on it.This review can deepen our understanding on molecular mechanism of myocardial ischemia thus to provide new drug targets and interventions for myocardial ischemia.
引文
[1]Swirski F K,Nahrendorf M.Leukocyte behavior in atherosclerosis,myocardial infarction,and heart failure.Science,2013,339(6116):161-166
[2]Lazzeroni D,Rimoldi O,Camici P G.From left ventricular hypertrophy to dysfunction and failure.Circulation Journal Official Journal of the Japanese Circulation Society,2016,80(3):555-564
[3]Cui Y C,Pan C S,Yan L,et al.Ginsenoside Rb1 protects against ischemia/reperfusion-induced myocardial injury via energy metabolism regulation mediated by RhoA signaling pathway.Scientific Reports,2017,7:44579
[4]Lal H,Ahmad F,Woodgett J,et al.The GSK-3 family as therapeutic target for myocardial diseases.Circulation Research,2015,116(1):138-149
[5]Boengler K,Kosiol M,Mayr M,et al.Mitochondria and ageing:Role in heart,skeletal muscle and adipose tissue.Journal of Cachexia,Sarcopenia and Muscle,2017,8(3):349-369
[6]Qi D,Young L H.AMPK:energy sensor and survival mechanism in the ischemic heart.Trends in Endocrinology&Metabolism,2015,26(8):422-429
[7]Shirai T,Nazarewicz R R,Wallis B B,et al.The glycolytic enzyme PKM2 bridges metabolic and inflammatory dysfunction in coronary artery disease.Journal of Experimental Medicine,2016,213(3):337-354
[8]Yu L,Bing G,Duan W,et al.Melatonin ameliorates myocardial ischemia/reperfusion injury in type 1 diabetic rats by preserving mitochondrial function:Role of AMPK-PGC-1α-SIRT3 signaling.Scientific Reports,2017,7:41337
[9]Hao M,Zhu S,Hu L,et al.Myocardial ischemic postconditioning promotes autophagy against ischemia reperfusion injury via the activation of the nNOS/AMPK/mTOR pathway.International Journal of Molecular Sciences,2017,18(3):614
[10]Lin Y R,Li C J,Syu S H,et al.Early administration of glutamine protects cardiomyocytes from post-cardiac arrest acidosis.Biomed Research International,2016,2016(10):2106342
[11]Samovski D,Su X,Xu Y,et al.Insulin and AMPK regulate FA translocase/CD36 plasma membrane recruitment in cardiomyocytes via Rab GAP AS160 and Rab8a Rab GTPase.Journal of Lipid Research,2012,53(4):709-717
[12]Novikova D S,Garabadzhiu A V,Melino G,et al.AMP-activated protein kinase:Structure,function,and role in pathological processes.Biochemistry,2015,80(2):127-144
[13]Majd S,Power J H,Koblar S A,et al.Early glycogen synthase kinase-3βand protein phosphatase 2A independent tau dephosphorylation during global brain ischaemia and reperfusion following cardiac arrest and the role of the adenosine monophosphate kinase pathway.European Journal of Neuroscience,2016,44(3):1987-1997
[14]张倩,张怡,卢令慧,等.PPARs在冠心病脂质代谢和炎性反应中分子调控机制及中医药研究进展.中华中医药杂志,2017,32(8):3623-3625
[15]Radika M K,Anuradha C V.Activation of insulin signaling and energy sensing network by AICAR,an AMPK activator in insulin resistant rat tissues.Journal of Basic&Clinical Physiology&Pharmacology,2015,26(6):563-574
[16]陈标,满玉蓉,高柳玲,等.AMPK调控能量代谢研究进展.生物学杂志,2017,34(5):78-82
[17]Ma N,Bai J,Zhang W,et al.Trimetazidine protects against cardiac ischemia/reperfusion injury via effects on cardiac miRNA-21expression,Akt and the Bcl-2/Bax pathway.Molecular Medicine Reports,2016,14(5):4216-4222
[18]张凤娟.糖代谢机制在丹参酮ⅡA和姜黄素抑制食管癌细胞增殖的作用研究.北京:北京工业大学,2016
[19]Wu C,Guo Y,Su Y,et al.Cordycepin activates AMP-activated protein kinase(AMPK)via,interaction with theγ1 subunit.Journal of Cellular&Molecular Medicine,2014,18(2):293-304
[20]Chang W,Zhang M,Meng Z,et al.Berberine treatment prevents cardiac dysfunction and remodeling through activation of5’-adenosine monophosphate-activated protein kinase in type 2diabetic rats and in palmitate-induced hypertrophic H9c2 cells.European Journal of Pharmacology,2015,769(14):55-63
[21]龚婉.丹参酚酸/三七皂苷配伍抗心肌缺氧损伤的作用机制研究.杭州:浙江大学,2013
[22]李艺.GS Rb1与IA对缺血缺氧心肌细胞的作用及机理探究.广州:广州中医药大学,2016
[23]张萌.降糖三黄片干预2型糖尿病大鼠糖脂代谢AMPK通路的实验研究.广州:广州中医药大学,2015
[24]Hong C,Wang Q,Shi T,et al.Effect of DanQi Pill on PPARα,lipid disorders and arachidonic acid pathway in rat model of coronary heart disease.BMC Complementary and Alternative Medicine,2016,16(1):1-10
[25]楼丹飞,曹敏,王佑华,等.超微细粉小复方对心肌缺血/再灌注损伤大鼠AMPK、GLUT4 mRNA的影响.四川中医,2011,29(11):30-32
[26]武建功.益气活血方基于Notch信号调控心肌梗死后心肌重构作用机理的研究.北京:北京中医药大学,2017
[27]舒华.温阳振衰颗粒联合运动训练对慢性心衰大鼠心肌能量代谢的影响.长沙:湖南中医药大学,2016
[2]Lazzeroni D,Rimoldi O,Camici P G.From left ventricular hypertrophy to dysfunction and failure.Circulation Journal Official Journal of the Japanese Circulation Society,2016,80(3):555-564
[3]Cui Y C,Pan C S,Yan L,et al.Ginsenoside Rb1 protects against ischemia/reperfusion-induced myocardial injury via energy metabolism regulation mediated by RhoA signaling pathway.Scientific Reports,2017,7:44579
[4]Lal H,Ahmad F,Woodgett J,et al.The GSK-3 family as therapeutic target for myocardial diseases.Circulation Research,2015,116(1):138-149
[5]Boengler K,Kosiol M,Mayr M,et al.Mitochondria and ageing:Role in heart,skeletal muscle and adipose tissue.Journal of Cachexia,Sarcopenia and Muscle,2017,8(3):349-369
[6]Qi D,Young L H.AMPK:energy sensor and survival mechanism in the ischemic heart.Trends in Endocrinology&Metabolism,2015,26(8):422-429
[7]Shirai T,Nazarewicz R R,Wallis B B,et al.The glycolytic enzyme PKM2 bridges metabolic and inflammatory dysfunction in coronary artery disease.Journal of Experimental Medicine,2016,213(3):337-354
[8]Yu L,Bing G,Duan W,et al.Melatonin ameliorates myocardial ischemia/reperfusion injury in type 1 diabetic rats by preserving mitochondrial function:Role of AMPK-PGC-1α-SIRT3 signaling.Scientific Reports,2017,7:41337
[9]Hao M,Zhu S,Hu L,et al.Myocardial ischemic postconditioning promotes autophagy against ischemia reperfusion injury via the activation of the nNOS/AMPK/mTOR pathway.International Journal of Molecular Sciences,2017,18(3):614
[10]Lin Y R,Li C J,Syu S H,et al.Early administration of glutamine protects cardiomyocytes from post-cardiac arrest acidosis.Biomed Research International,2016,2016(10):2106342
[11]Samovski D,Su X,Xu Y,et al.Insulin and AMPK regulate FA translocase/CD36 plasma membrane recruitment in cardiomyocytes via Rab GAP AS160 and Rab8a Rab GTPase.Journal of Lipid Research,2012,53(4):709-717
[12]Novikova D S,Garabadzhiu A V,Melino G,et al.AMP-activated protein kinase:Structure,function,and role in pathological processes.Biochemistry,2015,80(2):127-144
[13]Majd S,Power J H,Koblar S A,et al.Early glycogen synthase kinase-3βand protein phosphatase 2A independent tau dephosphorylation during global brain ischaemia and reperfusion following cardiac arrest and the role of the adenosine monophosphate kinase pathway.European Journal of Neuroscience,2016,44(3):1987-1997
[14]张倩,张怡,卢令慧,等.PPARs在冠心病脂质代谢和炎性反应中分子调控机制及中医药研究进展.中华中医药杂志,2017,32(8):3623-3625
[15]Radika M K,Anuradha C V.Activation of insulin signaling and energy sensing network by AICAR,an AMPK activator in insulin resistant rat tissues.Journal of Basic&Clinical Physiology&Pharmacology,2015,26(6):563-574
[16]陈标,满玉蓉,高柳玲,等.AMPK调控能量代谢研究进展.生物学杂志,2017,34(5):78-82
[17]Ma N,Bai J,Zhang W,et al.Trimetazidine protects against cardiac ischemia/reperfusion injury via effects on cardiac miRNA-21expression,Akt and the Bcl-2/Bax pathway.Molecular Medicine Reports,2016,14(5):4216-4222
[18]张凤娟.糖代谢机制在丹参酮ⅡA和姜黄素抑制食管癌细胞增殖的作用研究.北京:北京工业大学,2016
[19]Wu C,Guo Y,Su Y,et al.Cordycepin activates AMP-activated protein kinase(AMPK)via,interaction with theγ1 subunit.Journal of Cellular&Molecular Medicine,2014,18(2):293-304
[20]Chang W,Zhang M,Meng Z,et al.Berberine treatment prevents cardiac dysfunction and remodeling through activation of5’-adenosine monophosphate-activated protein kinase in type 2diabetic rats and in palmitate-induced hypertrophic H9c2 cells.European Journal of Pharmacology,2015,769(14):55-63
[21]龚婉.丹参酚酸/三七皂苷配伍抗心肌缺氧损伤的作用机制研究.杭州:浙江大学,2013
[22]李艺.GS Rb1与IA对缺血缺氧心肌细胞的作用及机理探究.广州:广州中医药大学,2016
[23]张萌.降糖三黄片干预2型糖尿病大鼠糖脂代谢AMPK通路的实验研究.广州:广州中医药大学,2015
[24]Hong C,Wang Q,Shi T,et al.Effect of DanQi Pill on PPARα,lipid disorders and arachidonic acid pathway in rat model of coronary heart disease.BMC Complementary and Alternative Medicine,2016,16(1):1-10
[25]楼丹飞,曹敏,王佑华,等.超微细粉小复方对心肌缺血/再灌注损伤大鼠AMPK、GLUT4 mRNA的影响.四川中医,2011,29(11):30-32
[26]武建功.益气活血方基于Notch信号调控心肌梗死后心肌重构作用机理的研究.北京:北京中医药大学,2017
[27]舒华.温阳振衰颗粒联合运动训练对慢性心衰大鼠心肌能量代谢的影响.长沙:湖南中医药大学,2016
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |