淫羊藿及其主要成分调节AMPK通路治疗心力衰竭研究进展
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摘要
在概述心力衰竭能量代谢特点的基础上,综述淫羊藿及其主要成分调节磷酸腺苷活化蛋白激酶(AMPK)通路治疗心力衰竭研究进展。研究发现,淫羊藿可通过调节AMPK通路的不同靶点治疗心力衰竭:可诱导过氧化物酶体增殖活化受体γ辅助活化因子1α(PGC-1α)的表达激活AMPK,促进能量产生;可调节葡萄糖转运体4(GLUT4)的生成和乙酰辅酶A羧化酶(ACC)表达,优化底物代谢,促进能量生成;可诱导过氧化物酶体增殖物激活受体α(PPARα)表达激活AMPK通路,调节能量生成;可抑制活性氧簇(ROS)产生,增加腺苷三磷酸(ATP)酶活性,提高能量利用。
This review summarizes the research progress of Herba Epimedii and its main components in regulating AMPK pathway in the treatment of heart failure. It has been found that Epimedium can prevent heart failure by regulating different targets in the AMPK pathway: activate AMPK to promote energy generation through regulation of the PGC-1α and PPARα expression; and regulate the expression of GLUT4 and ACC to optimize substrate metabolism and stimulate energy generation. It also can inhibit ROS production and increase ATPase activity to improve energy utilization.
This review summarizes the research progress of Herba Epimedii and its main components in regulating AMPK pathway in the treatment of heart failure. It has been found that Epimedium can prevent heart failure by regulating different targets in the AMPK pathway: activate AMPK to promote energy generation through regulation of the PGC-1α and PPARα expression; and regulate the expression of GLUT4 and ACC to optimize substrate metabolism and stimulate energy generation. It also can inhibit ROS production and increase ATPase activity to improve energy utilization.
引文
[1]JIANG H,GE J.Epidemiology and clinical management of cardiomyopathies and heart failure in China[J].Heart,2009,95(21):1727-1731.
[2]MCMURRAY J J,PACKER M,DESAI A S,et al.Dual angiotensin receptor and neprilysin inhibition as an alternative to angiotensinconverting enzyme inhibition in patients with chronic systolic heart failure:rationale for and design of the Prospective comparison of ARNIwith ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial(PARADIGM-HF)[J].Eur J Heart Fail,2013,15(9):1602-1673.
[3]孙路路,吕蓉,梁涛,等.心力衰竭患者出院后1年内预后状况及影响因素分析[J].中国循环杂志,2013,28(2):125-128.
[4]SUN D,YANG F.Metformin improves cardiac function in mice with heart failure after myocardial infarction by regulating mitochondrial energy metabolism[J].Biochem Biophys Res Commun,2017,486(2):329-335.
[5]舒华,陈新宇.中药干预慢性心力衰竭心肌能量代谢治疗进展[J].中国老年学杂志,2017,37(3):742-745.
[6]董晓蕾,郭寒,赵智明,等.淫羊藿总黄酮对异丙基肾上腺素诱导心力衰竭大鼠醛固酮的影响[J].安徽医药,2010,14(2):136-139.
[7]李富饶,刘志忠,宋耀鸿.淫羊藿总黄酮对心力衰竭大鼠心肌细胞凋亡的调控作用研究[J].中国中医急症,2012,21(3):392-393,396.
[8]VAN BILSEN M,VAN NIEUWENHOVEN F A,VAN DER VUSSE GJ.Metabolic remodelling of the failing heart:beneficial or detrimental?[J].Cardiovasc Res,2009,81(3):420-428.
[9]WANG Y,LI C,CHUO W J,et al.Integrated proteomic and metabolomicanalysisreveals the NADH-mediated TCA cycle and energymetabolism disorders based on a new model ofchronic progressive heart failure[J].Mol Bio Syst,2013,9(12):3135-3145.
[10]AROOR A R,MANDAVIA C H,SOWERS J R.Insulin resistance and heart failure:molecular mechanisms[J].Heart Fail Clin,2012,8(4):609-617.
[11]SHEPHARD E G,ANDERSON R,ROSEN O,et al.C-reactive protein(CRP)peptides inactivate enolase in human neutrophils leading to depletion of intracellular ATP and inhibition of superoxide generation[J].Immunology,1992,76(1):79-85.
[12]SANZ P,RUBIO T,GARCIA-GIMENO M A.AMPKβsubunits:more than just a scaffold in the formation of AMPK complex[J].Febs Journal,2013,280(16):3723-3733.
[13]钟伟,于远望,王永刚,等.双参强心方对心力衰竭大鼠血流动力学和心肌能量代谢的影响[J].时珍国医国药,2015,26(9):2093-2095.
[14]杨海波,王小芳,赵晓燕,等.二甲双胍对心力衰竭大鼠心功能的影响及其机制[J].山东医药,2012,52(9):34-36.
[15]熊延路,王明星,韩勇,等.AMPK:细胞能量中枢[J].现代生物医学进展,2014,14(31):6190-6196.
[16]焦美钰,王佳豪,许亮,等.淫羊藿本草考证与中国淫羊藿属植物分类研究[J].中国中医药现代远程教育,2017,15(14):157-160.
[17]李艳,于涛,苗明三.淫羊藿的化学、药理与临床应用分析[J].中医学报,2017,32(4):619-622.
[18]王焕珍,柴艺汇,陈云志,等.淫羊藿化学成分与药理作用研究进展[J].亚太传统医药,2016,12(7):63-65.
[19]杨如会,徐旖旎,沈祥春.淫羊藿苷对去卵巢肥胖大鼠体质量和脂质代谢的影响[J].中药材,2015,38(9):1946-1949.
[20]李雯娴,邓媛媛,石京山,等.淫羊藿苷上调PPARα和PGC-1α蛋白的表达改善慢性脑低灌注大鼠模型的空间学习记忆[J].遵义医学院学报,2014,37(6):591-594.
[21]胡保印.淫羊藿苷抗Ⅱ型糖尿病效果评价及机理研究[D].青岛:青岛大学,2016.
[22]包慧兰,陈黎.淫羊藿苷抗糖尿病大鼠心肌线粒体氧化应激损伤作用研究[J].中国中药杂志,2011,36(11):1503-1507.
[23]ZHOU D Y,SU Y,GAO P,et al.Resveratrol ameliorates high glucoseinduced oxidative stress injury in human umbilical vein endothelial cells by activating AMPK[J].Life Sciences,2015,136(9):94-99.
[24]王秋娟,潘志伟,杨涓,等.淫羊藿总黄酮不同给药途径对实验性心肌缺血的影响[J].中国临床药理学与治疗学,2007,12(7):794-799.
[25]李靳,邓丽丽,周志勇,等.三七总皂苷联合淫羊藿总黄酮改善D-gal致H9c2大鼠心肌细胞衰老的保护作用[J].中国中药杂志,2017,42(3):555-561.
[26]付亮,袁璟亚,丁春邦,等.淫羊藿药渣中多糖的提取及其体外抗氧化活性评价[J].食品工业科技,2016,37(1):116-120.
[27]张丽梅,杨竞,李意奇,等.淫羊藿苷抑制TGF-β1/Smad2信号通路改善压力超负荷所致的大鼠心肌纤维化[J].中国药理学通报,2013,29(10):1422-1425.
[28]王颖婉,李叶丽,李意奇,等.淫羊藿苷通过降低MMP-9抗自发性高血压大鼠心室重构[J].遵义医学院学报,2014,37(2):170-172,177.
[29]汪晶晶,唐其柱,王腾,等.淫羊藿苷对兔心室肌细胞L-型钙电流的影响[J].武汉大学学报(医学版),2007,28(3):282-286.
[30]尹晓飞,李冬梅,蔡大伟,等.淫羊藿总黄酮对小鼠心肌缺氧的保护作用[J].中国医院药学杂志,2008,28(4):283-284.
[31]QI D,YOUNG L H.AMPK:energy sensor and survival mechanismin the ischemic heart[J],Trends Endocrin Metab,2015,26(8):422-429.
[32]JGER S,HANDSCHIN C,STPIERRE J,et al.AMP-activated protein kinase(AMPK)action in skeletal muscle via direct phosphorylation of PGC-1alpha.[J].Proceedings of the National Academy of Sciences of the United States of America,2007,104(29):12017-12022.
[33]王江,高峰,聂凌,等.心力衰竭大鼠心肌组织PGC-1α表达变化及与能量代谢的关系[J].心脏杂志,2011,23(6):834.
[34]祝善俊,宋跃明,李隆贵,等.心力衰竭时心肌能量代谢的初步研究[J].中华心血管病杂志,1995,23(2):104-106.
[35]李靳,邓丽丽,周志勇,等.三七总皂苷联合淫羊藿总黄酮改善D-gal致H9c2大鼠心肌细胞衰老的保护作用[J].中国中药杂志,2017,42(3):555-561.
[36]KERNER J,HOPPEL C.Fatty acid import into mitochondria[J].Biochim Biophys Acta,2000,1486(1):1-17.
[37]MADRAZO J A,KELLY D P.The PPAR trio:regulators of myocardial energy metabolism in health and disease[J].J Mol Cell Cardiol,2008,44(6):968-975.
[38]王颖婉,李叶丽,王俊逸,等.PPARα、PPARγ的上调参与淫羊藿苷对自发性高血压大鼠心室重构的调节[J].中国药理学通报,2015,31(8):1117-1120.
[39]MNZEL T,CAMICI G G,MAACK C,et al.Impact of Oxidative Stress on the Heart and Vasculature:Part 2 of a 3-Part Series[J].J Am Coll Cardiol,2017,70(2):212-229.
[40]李丹,李蓓,石亚楠,等.心力衰竭与活性氧关系研究进展[J].中华实用诊断与治疗杂志,2013,27(1):8-10.
[41]沈磊,吴玉林.淫羊藿总黄酮对谷氨酸和咖啡因损伤PC12细胞的保护作用[J].中成药,2017,39(6):1268-1271.
[42]朱辉.补肾中药对地塞米松诱导肾虚骨质疏松症大鼠肾组织Ca2+-ATP酶含量的影响[C]//中国老年学学会骨质疏松委员会.2009年“健康骨骼”厦门论坛暨第十四届全国骨质疏松年会和第十一届全国钙剂年会会议文集.北京:中国骨质疏松杂志社,2009:2.
[2]MCMURRAY J J,PACKER M,DESAI A S,et al.Dual angiotensin receptor and neprilysin inhibition as an alternative to angiotensinconverting enzyme inhibition in patients with chronic systolic heart failure:rationale for and design of the Prospective comparison of ARNIwith ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial(PARADIGM-HF)[J].Eur J Heart Fail,2013,15(9):1602-1673.
[3]孙路路,吕蓉,梁涛,等.心力衰竭患者出院后1年内预后状况及影响因素分析[J].中国循环杂志,2013,28(2):125-128.
[4]SUN D,YANG F.Metformin improves cardiac function in mice with heart failure after myocardial infarction by regulating mitochondrial energy metabolism[J].Biochem Biophys Res Commun,2017,486(2):329-335.
[5]舒华,陈新宇.中药干预慢性心力衰竭心肌能量代谢治疗进展[J].中国老年学杂志,2017,37(3):742-745.
[6]董晓蕾,郭寒,赵智明,等.淫羊藿总黄酮对异丙基肾上腺素诱导心力衰竭大鼠醛固酮的影响[J].安徽医药,2010,14(2):136-139.
[7]李富饶,刘志忠,宋耀鸿.淫羊藿总黄酮对心力衰竭大鼠心肌细胞凋亡的调控作用研究[J].中国中医急症,2012,21(3):392-393,396.
[8]VAN BILSEN M,VAN NIEUWENHOVEN F A,VAN DER VUSSE GJ.Metabolic remodelling of the failing heart:beneficial or detrimental?[J].Cardiovasc Res,2009,81(3):420-428.
[9]WANG Y,LI C,CHUO W J,et al.Integrated proteomic and metabolomicanalysisreveals the NADH-mediated TCA cycle and energymetabolism disorders based on a new model ofchronic progressive heart failure[J].Mol Bio Syst,2013,9(12):3135-3145.
[10]AROOR A R,MANDAVIA C H,SOWERS J R.Insulin resistance and heart failure:molecular mechanisms[J].Heart Fail Clin,2012,8(4):609-617.
[11]SHEPHARD E G,ANDERSON R,ROSEN O,et al.C-reactive protein(CRP)peptides inactivate enolase in human neutrophils leading to depletion of intracellular ATP and inhibition of superoxide generation[J].Immunology,1992,76(1):79-85.
[12]SANZ P,RUBIO T,GARCIA-GIMENO M A.AMPKβsubunits:more than just a scaffold in the formation of AMPK complex[J].Febs Journal,2013,280(16):3723-3733.
[13]钟伟,于远望,王永刚,等.双参强心方对心力衰竭大鼠血流动力学和心肌能量代谢的影响[J].时珍国医国药,2015,26(9):2093-2095.
[14]杨海波,王小芳,赵晓燕,等.二甲双胍对心力衰竭大鼠心功能的影响及其机制[J].山东医药,2012,52(9):34-36.
[15]熊延路,王明星,韩勇,等.AMPK:细胞能量中枢[J].现代生物医学进展,2014,14(31):6190-6196.
[16]焦美钰,王佳豪,许亮,等.淫羊藿本草考证与中国淫羊藿属植物分类研究[J].中国中医药现代远程教育,2017,15(14):157-160.
[17]李艳,于涛,苗明三.淫羊藿的化学、药理与临床应用分析[J].中医学报,2017,32(4):619-622.
[18]王焕珍,柴艺汇,陈云志,等.淫羊藿化学成分与药理作用研究进展[J].亚太传统医药,2016,12(7):63-65.
[19]杨如会,徐旖旎,沈祥春.淫羊藿苷对去卵巢肥胖大鼠体质量和脂质代谢的影响[J].中药材,2015,38(9):1946-1949.
[20]李雯娴,邓媛媛,石京山,等.淫羊藿苷上调PPARα和PGC-1α蛋白的表达改善慢性脑低灌注大鼠模型的空间学习记忆[J].遵义医学院学报,2014,37(6):591-594.
[21]胡保印.淫羊藿苷抗Ⅱ型糖尿病效果评价及机理研究[D].青岛:青岛大学,2016.
[22]包慧兰,陈黎.淫羊藿苷抗糖尿病大鼠心肌线粒体氧化应激损伤作用研究[J].中国中药杂志,2011,36(11):1503-1507.
[23]ZHOU D Y,SU Y,GAO P,et al.Resveratrol ameliorates high glucoseinduced oxidative stress injury in human umbilical vein endothelial cells by activating AMPK[J].Life Sciences,2015,136(9):94-99.
[24]王秋娟,潘志伟,杨涓,等.淫羊藿总黄酮不同给药途径对实验性心肌缺血的影响[J].中国临床药理学与治疗学,2007,12(7):794-799.
[25]李靳,邓丽丽,周志勇,等.三七总皂苷联合淫羊藿总黄酮改善D-gal致H9c2大鼠心肌细胞衰老的保护作用[J].中国中药杂志,2017,42(3):555-561.
[26]付亮,袁璟亚,丁春邦,等.淫羊藿药渣中多糖的提取及其体外抗氧化活性评价[J].食品工业科技,2016,37(1):116-120.
[27]张丽梅,杨竞,李意奇,等.淫羊藿苷抑制TGF-β1/Smad2信号通路改善压力超负荷所致的大鼠心肌纤维化[J].中国药理学通报,2013,29(10):1422-1425.
[28]王颖婉,李叶丽,李意奇,等.淫羊藿苷通过降低MMP-9抗自发性高血压大鼠心室重构[J].遵义医学院学报,2014,37(2):170-172,177.
[29]汪晶晶,唐其柱,王腾,等.淫羊藿苷对兔心室肌细胞L-型钙电流的影响[J].武汉大学学报(医学版),2007,28(3):282-286.
[30]尹晓飞,李冬梅,蔡大伟,等.淫羊藿总黄酮对小鼠心肌缺氧的保护作用[J].中国医院药学杂志,2008,28(4):283-284.
[31]QI D,YOUNG L H.AMPK:energy sensor and survival mechanismin the ischemic heart[J],Trends Endocrin Metab,2015,26(8):422-429.
[32]JGER S,HANDSCHIN C,STPIERRE J,et al.AMP-activated protein kinase(AMPK)action in skeletal muscle via direct phosphorylation of PGC-1alpha.[J].Proceedings of the National Academy of Sciences of the United States of America,2007,104(29):12017-12022.
[33]王江,高峰,聂凌,等.心力衰竭大鼠心肌组织PGC-1α表达变化及与能量代谢的关系[J].心脏杂志,2011,23(6):834.
[34]祝善俊,宋跃明,李隆贵,等.心力衰竭时心肌能量代谢的初步研究[J].中华心血管病杂志,1995,23(2):104-106.
[35]李靳,邓丽丽,周志勇,等.三七总皂苷联合淫羊藿总黄酮改善D-gal致H9c2大鼠心肌细胞衰老的保护作用[J].中国中药杂志,2017,42(3):555-561.
[36]KERNER J,HOPPEL C.Fatty acid import into mitochondria[J].Biochim Biophys Acta,2000,1486(1):1-17.
[37]MADRAZO J A,KELLY D P.The PPAR trio:regulators of myocardial energy metabolism in health and disease[J].J Mol Cell Cardiol,2008,44(6):968-975.
[38]王颖婉,李叶丽,王俊逸,等.PPARα、PPARγ的上调参与淫羊藿苷对自发性高血压大鼠心室重构的调节[J].中国药理学通报,2015,31(8):1117-1120.
[39]MNZEL T,CAMICI G G,MAACK C,et al.Impact of Oxidative Stress on the Heart and Vasculature:Part 2 of a 3-Part Series[J].J Am Coll Cardiol,2017,70(2):212-229.
[40]李丹,李蓓,石亚楠,等.心力衰竭与活性氧关系研究进展[J].中华实用诊断与治疗杂志,2013,27(1):8-10.
[41]沈磊,吴玉林.淫羊藿总黄酮对谷氨酸和咖啡因损伤PC12细胞的保护作用[J].中成药,2017,39(6):1268-1271.
[42]朱辉.补肾中药对地塞米松诱导肾虚骨质疏松症大鼠肾组织Ca2+-ATP酶含量的影响[C]//中国老年学学会骨质疏松委员会.2009年“健康骨骼”厦门论坛暨第十四届全国骨质疏松年会和第十一届全国钙剂年会会议文集.北京:中国骨质疏松杂志社,2009:2.