参芪益心方对H9C2心肌细胞能量代谢的影响及机制研究
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摘要
目的：观察参芪益心方对去甲肾上腺素诱导H9C2大鼠心肌细胞的保护作用,研究参芪益心方对于受损心肌细胞能量代谢的调节,探讨参芪益心方治疗心力衰竭的作用机制。
方法：H9C2大鼠心肌细胞分为正常对照组、模型组、曲美他嗪组,参芪益心组。后3组分别加入正常大鼠血清10μ L、盐酸曲美他嗪含药血清10u L、参芪益心方含药血清10μL,各组均加入去甲肾上腺素(最终浓度均为2u mol/L),在加药后24小时,48小时进行指标检测及倒置显微镜观察,MTT法测定细胞存活率,闪烁荧光法检测心肌细胞脂肪酸,葡萄糖代谢率。高效液相色谱检测细胞能量合成情况,免疫印迹技术研究心肌细胞ATP合成酶F1亚单位及PPARa蛋白表达情况
结果：
与模型组比较,参芪益心方组和曲美他嗪组心肌存活率OD值显著升高(P<0.01),参芪益心方组显著高于曲美他嗪组(P<0.01);与模型组比较,参芪益心方组和曲美他嗪组心肌细胞脂肪酸氧化率显著下降(P<0.01),参芪益心方组显著低于曲美他嗪组(P<0.01)；葡萄糖氧化率和ATP合成量显著上升(P<0.01),参芪益心方组显著高于曲美他嗪组(P<0.01);与模型组和曲美他嗪组比较,参芪益心方组心肌细胞ATP合成酶F1亚单位表达显著上升,PPARa蛋白表达显著下调。
结论：
1、参芪益心方对去甲肾上腺素诱导的H9C2大鼠心肌细胞具有确切的保护作用。
2、参芪益心方能有效调节受损心肌细胞能量代谢,通过抑制PPARa的表达抑制脂肪酸代谢,使受损心肌细胞以葡萄糖氧化为主要能量来源,在耗氧相同的情况下高效合成ATP,维持心肌细胞代谢需要。
3、参芪益心方能有效保护心肌细胞线粒体膜电位水平,调节受损心肌细胞能量代谢,这可视为参芪益心方治疗慢性心力衰竭的主要机制。
Objective:To observe the protective effect of Shenqiyixin Recipe on H9C2cells induced by norepinephrine, and to investigate the Shenqiyixin Recipe's adjustment effect on energy metabolism of H9C2cells, explore the therapeutic mechanism of Shenqiyixin Recipe on heart failure.
Methods:H9C2rat cardiomyocytes were divided into normal control group, model group, Trimetazidine group and Shenqiyixin group. The last three groups were added with normal rat serum10μL, serum with10μL Trimetazidine, serum with10μL Shenqiyixin Recipe and each group added norepinephrine (final concentration was2umol/L), indicators were tested at the24h,48h. cardiomyocytes survival was detected by MTT,Metabolic rate of fatty acids and glucose were detected by blinking fluorescence,and HPLC were unutilized for detecting the ATP generation from damaged myocardial cell. immunoblotting were unutilized for detecting the expression of F1-ATPase、PPARa
Results:
compared with model group, Shenqiyixin Recipe group and Trimetazidine group could significantly increase OD value(P<0.01), the value of Shenqiyixin Recipe group was significantly higher than Trimetazidine group (P<0.01); compared with model group, the fatty metabolic rate of Shenqiyixin Recipe group and Trimetazidine group were significantly lower (P<0.01), and fatty metabolic rate of Shenqiyixin Recipe group was significantly lower than Trimetazidine group(P<0.01); the glucose metabolic rate of Shenqiyixin Recipe group and Trimetazidine group were significantly higher (P<0.01), and glucose metabolic rate of Shenqiyixin Recipe group was significantly higher than Trimetazidine group(P<0.01);compared with model group and Trimetazidine group. The expression of F1-ATPase in Shenqiyixin Recipe group was significantly higher and the expression of PPARa in Shenqiyixin Recipe group is significantly lower.
Conclusion:
1. Shenqiyixin Recipe could effectively protect the H9C2cells induced by norepinephrine.
2. Shenqiyixin Recipe could effectively adjust the energy metabolism of damaged cardiomyocytes. by inhibiting the expression of PPARa which down regulating the fatty acid metabolism, the damaged cardiomyocytes could generate ATP efficiently by the glucose metabolic way to maintain cardiomyocytes metabolism.
3. Shenqiyixin Recipe could effectively protect the cardiomyocytes'MMP and adjust the energy metabolism of damaged cardiomyocytes. It may be the mechanism for Shenqiyixin Recipe treating heart failure
方法：H9C2大鼠心肌细胞分为正常对照组、模型组、曲美他嗪组,参芪益心组。后3组分别加入正常大鼠血清10μ L、盐酸曲美他嗪含药血清10u L、参芪益心方含药血清10μL,各组均加入去甲肾上腺素(最终浓度均为2u mol/L),在加药后24小时,48小时进行指标检测及倒置显微镜观察,MTT法测定细胞存活率,闪烁荧光法检测心肌细胞脂肪酸,葡萄糖代谢率。高效液相色谱检测细胞能量合成情况,免疫印迹技术研究心肌细胞ATP合成酶F1亚单位及PPARa蛋白表达情况
结果：
与模型组比较,参芪益心方组和曲美他嗪组心肌存活率OD值显著升高(P<0.01),参芪益心方组显著高于曲美他嗪组(P<0.01);与模型组比较,参芪益心方组和曲美他嗪组心肌细胞脂肪酸氧化率显著下降(P<0.01),参芪益心方组显著低于曲美他嗪组(P<0.01)；葡萄糖氧化率和ATP合成量显著上升(P<0.01),参芪益心方组显著高于曲美他嗪组(P<0.01);与模型组和曲美他嗪组比较,参芪益心方组心肌细胞ATP合成酶F1亚单位表达显著上升,PPARa蛋白表达显著下调。
结论：
1、参芪益心方对去甲肾上腺素诱导的H9C2大鼠心肌细胞具有确切的保护作用。
2、参芪益心方能有效调节受损心肌细胞能量代谢,通过抑制PPARa的表达抑制脂肪酸代谢,使受损心肌细胞以葡萄糖氧化为主要能量来源,在耗氧相同的情况下高效合成ATP,维持心肌细胞代谢需要。
3、参芪益心方能有效保护心肌细胞线粒体膜电位水平,调节受损心肌细胞能量代谢,这可视为参芪益心方治疗慢性心力衰竭的主要机制。
Objective:To observe the protective effect of Shenqiyixin Recipe on H9C2cells induced by norepinephrine, and to investigate the Shenqiyixin Recipe's adjustment effect on energy metabolism of H9C2cells, explore the therapeutic mechanism of Shenqiyixin Recipe on heart failure.
Methods:H9C2rat cardiomyocytes were divided into normal control group, model group, Trimetazidine group and Shenqiyixin group. The last three groups were added with normal rat serum10μL, serum with10μL Trimetazidine, serum with10μL Shenqiyixin Recipe and each group added norepinephrine (final concentration was2umol/L), indicators were tested at the24h,48h. cardiomyocytes survival was detected by MTT,Metabolic rate of fatty acids and glucose were detected by blinking fluorescence,and HPLC were unutilized for detecting the ATP generation from damaged myocardial cell. immunoblotting were unutilized for detecting the expression of F1-ATPase、PPARa
Results:
compared with model group, Shenqiyixin Recipe group and Trimetazidine group could significantly increase OD value(P<0.01), the value of Shenqiyixin Recipe group was significantly higher than Trimetazidine group (P<0.01); compared with model group, the fatty metabolic rate of Shenqiyixin Recipe group and Trimetazidine group were significantly lower (P<0.01), and fatty metabolic rate of Shenqiyixin Recipe group was significantly lower than Trimetazidine group(P<0.01); the glucose metabolic rate of Shenqiyixin Recipe group and Trimetazidine group were significantly higher (P<0.01), and glucose metabolic rate of Shenqiyixin Recipe group was significantly higher than Trimetazidine group(P<0.01);compared with model group and Trimetazidine group. The expression of F1-ATPase in Shenqiyixin Recipe group was significantly higher and the expression of PPARa in Shenqiyixin Recipe group is significantly lower.
Conclusion:
1. Shenqiyixin Recipe could effectively protect the H9C2cells induced by norepinephrine.
2. Shenqiyixin Recipe could effectively adjust the energy metabolism of damaged cardiomyocytes. by inhibiting the expression of PPARa which down regulating the fatty acid metabolism, the damaged cardiomyocytes could generate ATP efficiently by the glucose metabolic way to maintain cardiomyocytes metabolism.
3. Shenqiyixin Recipe could effectively protect the cardiomyocytes'MMP and adjust the energy metabolism of damaged cardiomyocytes. It may be the mechanism for Shenqiyixin Recipe treating heart failure
引文
[1]Van BM,Smeets PJ,Gilde AJ,et al. Metabolic remodeling of the failing heart:the cardiac burn-out syndrome [J]. Cardiovasc Res.2004.61:218-226.
[2]Stanley WC, Recchia FA, Lopaschu k GD. Myocardial substrate metabol ism in the normal and failing heart [J] . Physiol Rev,2005,85:1093-1129.
[3]Taylor M, Wallhaus TR, Degrado TR, et al. An evaluation of myocardial fatty acid and glucose up take using PET with (18F)FDG in patient s with congestive heart failure [J]. J Nucl Med,2001,42:55-62.
[4]Aroor AR, Mandavia CH,Sowers JR.Insulin resistance and heart failure:molecular mechanisms [J]. Heart failure clin.2012.8 (4):609-17.
[5]Lewandowski ED. Cardiac carbon 13 magnetic resonance spectroscopy:on the horizon or over the rainbow [J]. J Nucl Cardiol,2002,9(4):419-428.
[6]Beer M, Seyfarth T, Sandstede J, et al. Absolute concent rations of high-energy phosphatemet abolites in normal, hypertrophied, and fail ing human myocardium measured non invasively with 31 P- SLOOP magnetic resonance spectroscopy [J]. J Am Coll Cardiol,2002,40 (7):1267- 1274.
[7]Bilsen M, Smeets P, Gilde A, et al. Metabolic remodeling of the failing heart:the cardiac burn-out syndrome[J]. Cardiovasc Res,2004,61 (2):218-226.
[8]Lionetti V, Stnnley WC, Recchia F. Modulating fatty acid oxidation in heart failure[J]. Cardiovasc Res,2011,90(2):202-209.
[9]Arany Z, He H, Lin J, et al. Transcriptional coactivator PGC-1 a controls the energy state and contractile function of cardiac muscle[J].Cell Metab,2005, 1(4):259-271.
[10]李良刚,陈槐卿CaMK和AMPK信号通路能共调收缩信号诱导的骨骼肌细胞GLUT4基因转录[J].生物化学与生物物理进展,2009:4:471-9.
[11]Marsin AS, Bertrand L, Rider MH, et al. Phosphorylation andactivation of heart PFK-2 by AMPK has a role in the stimulation of glycolysis during ischaemia[J]. Curr Biol,2000,10(20):1247-1255.
[12]刘小永,楚天舒.冠心病患者冠状动脉病变积分与血清游离脂肪酸的相关性分析[J]Clin Cardiol(China),2011,27(5):364-366.
[13]Beadle RM,Williams LK,Abozguia K,et al.Metabolic manipulation in chronic heart failure:study protocol for a randomized eontrolled trial [J].Trials,2011:12:140.
[14]Halbirk M.Norrelund H.Moller N,et al. Suppression of circulating free fatty acids with acipimox in chronic heart failure patients changes whole body metabolism but does not affect cardiac function [J]. AmJPhysiol Herrt Circ Physiol,2010,299(4): H1220- 1225.
[15]Lalloyer F,Stacls B,Fibrates,glitazones,and peroxisome proliferator-activated receptors [J]. Arterioscler Thromb VascBiol,2010,30(5),894-899.
[16]马瑞莲,姚震,何喜民PPAR-a与心血管疾病关系的基础研究进展[J].海南医学,2011,22(3)：28-30.
[17]Hamblin M,Chang L,Fan Y,et al.PPARs and the cardiovascular system[J].Antioxid Redox Signal,2009,11 (6):1415-1452.
[18]杜永才PPAR-a与动脉粥样硬化关系的研究进展[J].中国热带医学,2009,9(1):175—179.
[19]Van den Borne SW,Diez J,Blank esteijn WM,et al.Myocardial remodeling after infarction:the role of myofibroblasts[J]. Nat Rev Cardiol,2010,7(1):30-37.
[20]李萍,江珊.瑞舒伐他汀对大鼠肥厚心肌组织PPAR-Y和NF-k B蛋白表达的影响[J].中国老年学杂志,2012,3(32)：1007-1009.
[21]Elangbam CS, Tyler RD, Light foot RM. Peroxis ome proliferator-activated recept ors in atherosclerosis and inflammation-an update[J]. Toxicol Pathol,2001,29(2) 224-231.
[22]艾丽萍.洋地黄在心力衰竭中的应用[J].中国实用医药,2012,7(11):144.
[23]尹慧娟,黄淑田,张丽娜,等。慢性心力衰竭患者住院期间药物使用情况分析[J].中西医结合心脑血管病杂志,2011,29(11),1297-1299.
[24]贾岩,孙继华.浅谈血管紧张素转换酶抑制剂在心血管中应用[J].中国现代药物应用,2009,3(13):79-80.
[25]何斌.雷米普利联合美托洛尔治疗慢性充血性心力衰竭疗效观察60例[J].中国医药指南,2010,8(29):64-65.
[26]祁俊,俞学芳.美托洛尔治疗慢性充血性心力衰竭52例疗效观察[J].医学理论与实践,2010,23(5):534-535.
[27]肖磊.螺内酯治疗慢性心力衰竭的疗效观察[J].中国当代医药,2010,17(17)：56-58.
[28]张莉芳.醉固酮受体拮抗剂在慢性心力衰竭中的应用[J].中国现代药物应用,2012.6(11)：66-67.
[29]王强,薛成.醛固酮拮抗剂治疗慢性心力衰竭的临床疗效分析[J].中外医学研究,2010,8(7):68.
[30]邱晓燕.血浆水平在慢性心衰的诊断病情及预后评估中的应用价值[J].中西医结合心脑血管病杂志,2011,29(11):1299-1300.
[31]张春梅.重组人脑利钠治疗急性心肌梗死并心力衰竭58例疗效观察[J].临床医药实践,2012,21(5):355-357.
[32]董晋,于敬萍.重组人脑利钠肽和硝普钠治疗中重度慢性心力衰竭的对比研究[J].中西医结合心脑血管病杂志,2009,7(4):398-400.
[33]李庆洋.慢性心力衰竭的药物治疗进展及其现状[J].实用心脑肺血管病杂志,2012,20(6)：941.
[34]Morillas Blasco PJ, Hernandiz Martinez A, Azorin Villena I, et al Mitochondrial changes induced by trimetazidine in themyocardium. Med SciMonit[J].2005,11: 162-167.
[35]McClellan KJ, Plosker GL. Trimetazidine:Areview of its use in stable angina pectoris and other coronary conditions[J]. Drugs,1999,58:143-157.
[36]Ciapponi A, Pizarro R, Harrion J, et al. Cochrane Database Syst Rev,2005, 19(4):3614.
[37]沈宗泉,周亚峰.曲美他嗪在不稳定型心绞痛治疗中的临床应用研究.临床和实验医学杂志[J].2009,8(3)：75-76.
[38]Chiang GG, Seflon BM. Specific dephosphorylation of the lek tyrosine protein kinase at Tyr-394 by the SHP - 1 protein-tyrosinephos - phatase[J]. J Biol Chem, 2001,276(25):23173.
[39]Bonello L Sbragia P, Amabile N, et al. Protective effect of an a. cute oral loading dose of trimetazidine on myocardial injury following percutancous coronary intervention[J]. Heart,2007,93(6):703-707.
[40]KuHday F, Ahekin E, Yazlar AS, et al. Suppression of angioplas- tymlated inflammation by pro-procedural treatment with trimetazidine[J]. Tohoku J Exp Med, 2006,208(3):203-212.
[41]Tunerir B, Colak O, Alatas O, et al. Asian measurement of trop to detect eardioprotective effect of trimetasidine during coronary artery bypass grafting[J]. Ann Thorac Surg,1999,68:2173-2176.
[42]胡怡,张银香,殷巍国产曲美他嗪治疗成人急性病毒性心肌炎疗效观察[J]中国误诊学杂志,2008,21(8)：21.
[43]DiNapoli P, DiGiovanni P, Gaeta MA, et al. Trimetazidine and reduction in mortality and hospitalization in patients with ischemic dilated cardiomyopathy:a post hoc analysis of the Villa Pinid'Abruzzo Trimetazidine Trial[J].JCardiovasc Pharmaco,l 2007,50(5):585-589.
[44]Fragasso G, Perseghin G, DeCobelli F, et al. Effects of metabolic modulation by trimetazidine on left ventricular function and phosphocreatine/adenosine triphosphateratio in patients with heart failure[J]. Eur Heart J,2006,27(8):942-948.
[45]姜淑琴.心力衰竭的中医辨治[J].现代中西医结合杂志,2004;13(13):1799.
[46]叶盈,黄飞翔,吴耀中,等.健心颗粒治疗慢性心力衰竭65例临床观察[J].中医杂志,2006；47(1)：28.
[47]张持.中医对慢性充血性心力衰蝎的认识及治疗进展[J].吉林中医药,2006;26(11)：71-72.
[48]郑军.温阳利水法治疗慢性心力衰竭48例[J].陕西中医,2005,26(2):102-103.
[49]衡冲,兰宏民,席剑.参芪葶苈大枣汤为主治疗肺心病并心力衰竭35例[J].陕西中医,2002,23(2)：105-106.
[50]李丹萍,陈强,易莉,等.益气活血法对充血性心力衰竭患者疗效和心功能的影响[J].中国中西医结合杂志,2006.26(6)：552.
[51]李庆海.吕安清,张芳,等.参麦注射液对慢性充血性心力衰竭患者心率变异性的影响[J].中国中西医结合急救杂志.2000.7(5):273—275.
[52]郑艳秋.参麦注射液杏丁注射液并用治疗心功能不全20例[J].实用中医内科志.2005,19(2)：166—167.
[53]许晓乐,季晖,谷舒怡,等.黄芪甲苷对异丙肾上腺素所致小鼠心肌肥厚的保护作用[J].中国药科大学学报,2008,38(5)：451-455.
[54]石海莲,马春来,刘燕,等.黄芪皂苷甲抑制压力过载型心肌肥厚大鼠肾素血管紧张素的过度激活[J].中国中药杂.志,2009,34(24)：3242-3245.
[55]钟匕,杜九中,于小华,等.黄芪甲甙对病毒性心肌炎细胞凋亡作用的研究[J].南华大学学报医学版,2004,32(1)：17- 19.
[56]石海莲,刘燕,马春来,等.黄芪皂苷甲对高血压大鼠离体血管舒张功能及-氧化氮的影响[J].中国新药与临床杂志,2009,28(12)：905-906.
[57]刘燕,石海莲,马春来,等.黄芪皂苷甲对高血压大鼠血管肥厚及ET-1诱导离体血管收缩功能的影响[J].中国新药与临床杂志,2009,28(11):846-r 851.
[58]刘莉,刘丰,金娟.利心Ⅰ号对60例慢性心衰患者血浆BNP水平的影响[J].中医药学报,2003,31(3),7-8.
[59]顾焕,李霁,张久亮,等.益气活血法对慢性心力衰竭病TNF-a及Ang Ⅱ的影响[J].中西医结合心脑血管病杂志,2008,6(4),381-382.
[60]刘莉,胡思南,隋艳波,等.益气温阳活血利水法对充血性心力衰竭疗效观察及其对胰岛素抵抗的影响[J].陕西中医学院学报,2013,36(1),33-36.
[61]刘莉,邹国良,索传涛.利心Ⅰ号对CH F大鼠血流动力学、心肌细胞ICAM - 1基因蛋白表达的影响[J].心脏杂志,2007,19(2),166-169.
[62]刘莉,顾焕,邹国良,等.利心Ⅰ号对充血性心力衰竭大鼠心肌细胞Bax、Bcl-2表达的影响[J].中医药信息,2006,23(1),57-59.
[63]金娟,马林沁,邹国良,等.参芪益心方对慢性心力衰竭大鼠心肌组织Caspase-3及Caspase-9蛋白表达的影响[J].世界中西医结合杂志,2014,9(2),151-155.
[64]Ingwall JS. ATP and the heart [M].MA, USA:Kluwer Academic Publish ers,2002:197-216.
[65]Wang Z, Tang X, Li Y, et al.20-Hydroxyeicosa-tetraenoic acid inhibits the apoptotic responses inpulmonary artery smooth muscle cells[J]. Eur J Pharmacol, 2008,588(1):9-17.
[66]Hugel S, Horn M, Remkes H, et al. Showing results for preservation of cardiac function and energy reserve by the angiotensin converting enzyme inhibitor quinapril during postmyocardial infarction remodeling in the rat[J]. J Cardiovasc Magn Reson, 2001,3(3):215-225.
[67]邹旭,刘泽银,林晓忠,等.暖心胶囊治疗慢性心力衰竭远期疗效及生活质量 的观察[J].中国中西医结合杂志,2006,26(3)：269—270.
[68]李绍敏.补肾法治疗充血性心衰与益气法的对比研究[J].实用中医内科杂志.2005,19(5)：480.
[69]杨帆,赖沙毅.苠苈胶囊治疗慢性心衰68例[J].中国中西医结合杂杂志2007.27(11)：1041.
[70]于忠学,关丽梅,王炎焱,等.复方黄苠无糖颗粒对心肌缺血能量代谢的影响[J].中医药信息,2003,20(1)：55.
[71]林谦,于友华.党参对冠心病心绞痛患者的血液细胞及对小鼠心肌作用的定量细胞化学观察[J].中国组织化学与细胞化学杂志,1994,3(4):398.
[72]马晨,张善飞,曹彦光,等.丹参注射液对离体大鼠心肌能量代谢的调节作用[J].中国医科大学学报,2009,40(2)：147—151.
[73]张晶,王洪新,宋莹,等.黄芪甲苷抑制大鼠心肌肥厚及改善心肌能量代谢的作用观察[J].中成药,2012,34(5)：924-928.
[74]农一兵.从补益心气与改善心肌能量代谢的关系探讨慢性心力衰竭中西医结合研究的思路[J].中医杂志,2007,48(11)：1035-1036.
[75]高想,唐艳芬,蒋凤荣,等. 利心冲剂对心衰大鼠心肌细胞能量代谢的影响[J].中华中医药杂志,2010,25(10):1686.
[76]吴伟康.四逆汤与缺血心肌的能量代谢[J].中国中医基础医学杂志,1996,2(2)：26-28.
[77]殷惠军,蒋跃绒,刘颖,等.参桂胶囊对心肌细胞能量代谢及脂质过氧化影响的研究[J].中医药信息,2004,21(3)：71-73.
[78]陈琴.心复康口服液对心梗后心衰大鼠模型心功能及心肌能量代谢干预的研究[D].北京：北京中医药大学,2008.
[79]王万铁.川芎嗪对实验性缺血再灌注损伤心肌能量代谢的干预[J].中国急救医学,2003,23(3)：129-130.
[80]黄黎华,陈渊成,程昱,等.丹参水溶性成分含量变化对大鼠离体心肌能量代谢调节的影响[J].中国药科大学学报,2011,42(4)：348-353.
[81]王承龙,缪宇,殷惠军,等.西洋参茎叶总皂苷对急性心肌梗死大鼠心肌能量代谢的影响[J].中华老年心脑血管病杂志,2005,7(5)：341-343.
[82]高卫真,康毅,娄建石,等.黄芪苷对心肌细胞氧化损伤的保护作用[J].中国 心血管杂志,2005,10(3):1661-69.
[83]Sauvanet C. Duevzin_Caubet S.di Rago JP,et al. Energetic requirements and bioenergeic modulation of mitochondrial morphology and dynamics [J]. Semnin Cell Dev Biol.2.10,21(6):558-565.
[84]Skulachev VP. Mitochondrial filaments and clusters as intracellular power-transmitting cables[J]. Trends Biochem Sci.2001,26(1):23-29.
[85]Parone PA,Da CS,Tonders D,et al.Preventing mitochondrial fission impairs mitochondrial function and leads to loss of mitochondrial DNA[J], Plos One.2008, 3(9):e3257.
[86]Hom J,Sheu SS.Morphological dynamics of mitochondria a special emphasis on cardiac muscle cells[J]. J Mol Cell Cardiol.2009,46(6):811-820.
[87]Ostuni MA, P e ranzi G, Ducroc RA, et al. Distribution, pharmacological characterization and function of the 18 kDa translocator protein in rat small intestine [J]. Biol Cell,2009,101(10):573-86.
[88]Fulvio Celsi, Paola Pizzo, Marisa Brini, et al. Mitochondria, calcium and cell death:A deadly triad in neurodegeneration[J]. Biochim Biophys Acta,2009 1787(5):335-44.
[89]Javadov S, Karmazyn M, Escobales N. Mitochondrial Permeability Transition Pore Opening as a Promising Therapeutic Target in Cardiac Diseases[J]. J Pharmacol Exp Ther, 2009,330(3):670-8.
[90]Lukyanenko V, Chikando A, Lederer WJ. Mitochondria in cardiomyocyte Ca2+ signaling[J]. Int J Biochem Cell Biol,2009,41(10):1957-71.
[91]Griffiths EJ. Mitochondrial calcium transport in the heart:Physiological and pathological roles[J]. J Mol Cell Cardiol,2009,46(6):789-803.
[92]胡胡莲美,郑文岭,朴英杰.过氧化物酶体增殖物激活受体的医学重要性[J]. 医学分子生物杂志,2005,2(2):140-142.
[93]Torra IP, Chinetti G, Duval C, et al. Peroxisome proliferators-activated receptors: from transcriptional control to clinical practice[J].Curr Opin Lipidol,2001,12: 245-254.
[94]胡琴,李隆贵.心肌脂肪酸氧化酶的基因调控机制及PPAR α的作用[J].中国病理生理杂志,2002,18(12)：1552-1555.
[95]Unger RH. Lipotoxic diseases[J]. Annu Rev Med,2002,53:319-336.
[96]Ackerman SH,Tzagologg A,Function,structure and biogenesis of mitochondrial ATP synthase[J].Prog Nudeic Acid Res Mol Biol,2005,80:94.
[97]Haynes V,Traaseth NJ,Elfering S,et al.Nitration of specific tyro-sines in F0F1 ATP synthase and activity loss in aging[J].Am J Physiol Endocrinol Metab,2010,298(5): E978.
[98]Kane LA,Youngman MJ,Jensen Re,et al.Phosphorylation of the F0F1 ATP synthase beta subunit:functional and structural consequences assessed in a model system[J] Circ Res,2010,106(3):504.
[99]Unger RH, Orci L. Lipotoxic diseases of nonadipose tissue in obesity [J].Int J Obes Relat Metab Disord,2000,24(Suppl 4):S28-S32.
[100]刘平,于宁生,雷燕,等.关于血清药理学的若干思考[J].中国中西医结合杂志,1999,10(5)：263.
[101]杨胜利,何作云,冯兵,等.缺氧/复氧诱导培养人肥大心肌细胞凋亡模型的建立[J].重庆医学,2004,33(1)：4.
[102]米永杰,李健.中药血清药理学研究概述[J].四川解剖学杂志,2006,14(4)：35-36.
[103]周明眉,杨奎,姜远平等.中药血清药理学的方法研究——反应体系中含药血清加入量的研究[J].中药药理与临床,1998,14(6)：43-44.
[2]Stanley WC, Recchia FA, Lopaschu k GD. Myocardial substrate metabol ism in the normal and failing heart [J] . Physiol Rev,2005,85:1093-1129.
[3]Taylor M, Wallhaus TR, Degrado TR, et al. An evaluation of myocardial fatty acid and glucose up take using PET with (18F)FDG in patient s with congestive heart failure [J]. J Nucl Med,2001,42:55-62.
[4]Aroor AR, Mandavia CH,Sowers JR.Insulin resistance and heart failure:molecular mechanisms [J]. Heart failure clin.2012.8 (4):609-17.
[5]Lewandowski ED. Cardiac carbon 13 magnetic resonance spectroscopy:on the horizon or over the rainbow [J]. J Nucl Cardiol,2002,9(4):419-428.
[6]Beer M, Seyfarth T, Sandstede J, et al. Absolute concent rations of high-energy phosphatemet abolites in normal, hypertrophied, and fail ing human myocardium measured non invasively with 31 P- SLOOP magnetic resonance spectroscopy [J]. J Am Coll Cardiol,2002,40 (7):1267- 1274.
[7]Bilsen M, Smeets P, Gilde A, et al. Metabolic remodeling of the failing heart:the cardiac burn-out syndrome[J]. Cardiovasc Res,2004,61 (2):218-226.
[8]Lionetti V, Stnnley WC, Recchia F. Modulating fatty acid oxidation in heart failure[J]. Cardiovasc Res,2011,90(2):202-209.
[9]Arany Z, He H, Lin J, et al. Transcriptional coactivator PGC-1 a controls the energy state and contractile function of cardiac muscle[J].Cell Metab,2005, 1(4):259-271.
[10]李良刚,陈槐卿CaMK和AMPK信号通路能共调收缩信号诱导的骨骼肌细胞GLUT4基因转录[J].生物化学与生物物理进展,2009:4:471-9.
[11]Marsin AS, Bertrand L, Rider MH, et al. Phosphorylation andactivation of heart PFK-2 by AMPK has a role in the stimulation of glycolysis during ischaemia[J]. Curr Biol,2000,10(20):1247-1255.
[12]刘小永,楚天舒.冠心病患者冠状动脉病变积分与血清游离脂肪酸的相关性分析[J]Clin Cardiol(China),2011,27(5):364-366.
[13]Beadle RM,Williams LK,Abozguia K,et al.Metabolic manipulation in chronic heart failure:study protocol for a randomized eontrolled trial [J].Trials,2011:12:140.
[14]Halbirk M.Norrelund H.Moller N,et al. Suppression of circulating free fatty acids with acipimox in chronic heart failure patients changes whole body metabolism but does not affect cardiac function [J]. AmJPhysiol Herrt Circ Physiol,2010,299(4): H1220- 1225.
[15]Lalloyer F,Stacls B,Fibrates,glitazones,and peroxisome proliferator-activated receptors [J]. Arterioscler Thromb VascBiol,2010,30(5),894-899.
[16]马瑞莲,姚震,何喜民PPAR-a与心血管疾病关系的基础研究进展[J].海南医学,2011,22(3)：28-30.
[17]Hamblin M,Chang L,Fan Y,et al.PPARs and the cardiovascular system[J].Antioxid Redox Signal,2009,11 (6):1415-1452.
[18]杜永才PPAR-a与动脉粥样硬化关系的研究进展[J].中国热带医学,2009,9(1):175—179.
[19]Van den Borne SW,Diez J,Blank esteijn WM,et al.Myocardial remodeling after infarction:the role of myofibroblasts[J]. Nat Rev Cardiol,2010,7(1):30-37.
[20]李萍,江珊.瑞舒伐他汀对大鼠肥厚心肌组织PPAR-Y和NF-k B蛋白表达的影响[J].中国老年学杂志,2012,3(32)：1007-1009.
[21]Elangbam CS, Tyler RD, Light foot RM. Peroxis ome proliferator-activated recept ors in atherosclerosis and inflammation-an update[J]. Toxicol Pathol,2001,29(2) 224-231.
[22]艾丽萍.洋地黄在心力衰竭中的应用[J].中国实用医药,2012,7(11):144.
[23]尹慧娟,黄淑田,张丽娜,等。慢性心力衰竭患者住院期间药物使用情况分析[J].中西医结合心脑血管病杂志,2011,29(11),1297-1299.
[24]贾岩,孙继华.浅谈血管紧张素转换酶抑制剂在心血管中应用[J].中国现代药物应用,2009,3(13):79-80.
[25]何斌.雷米普利联合美托洛尔治疗慢性充血性心力衰竭疗效观察60例[J].中国医药指南,2010,8(29):64-65.
[26]祁俊,俞学芳.美托洛尔治疗慢性充血性心力衰竭52例疗效观察[J].医学理论与实践,2010,23(5):534-535.
[27]肖磊.螺内酯治疗慢性心力衰竭的疗效观察[J].中国当代医药,2010,17(17)：56-58.
[28]张莉芳.醉固酮受体拮抗剂在慢性心力衰竭中的应用[J].中国现代药物应用,2012.6(11)：66-67.
[29]王强,薛成.醛固酮拮抗剂治疗慢性心力衰竭的临床疗效分析[J].中外医学研究,2010,8(7):68.
[30]邱晓燕.血浆水平在慢性心衰的诊断病情及预后评估中的应用价值[J].中西医结合心脑血管病杂志,2011,29(11):1299-1300.
[31]张春梅.重组人脑利钠治疗急性心肌梗死并心力衰竭58例疗效观察[J].临床医药实践,2012,21(5):355-357.
[32]董晋,于敬萍.重组人脑利钠肽和硝普钠治疗中重度慢性心力衰竭的对比研究[J].中西医结合心脑血管病杂志,2009,7(4):398-400.
[33]李庆洋.慢性心力衰竭的药物治疗进展及其现状[J].实用心脑肺血管病杂志,2012,20(6)：941.
[34]Morillas Blasco PJ, Hernandiz Martinez A, Azorin Villena I, et al Mitochondrial changes induced by trimetazidine in themyocardium. Med SciMonit[J].2005,11: 162-167.
[35]McClellan KJ, Plosker GL. Trimetazidine:Areview of its use in stable angina pectoris and other coronary conditions[J]. Drugs,1999,58:143-157.
[36]Ciapponi A, Pizarro R, Harrion J, et al. Cochrane Database Syst Rev,2005, 19(4):3614.
[37]沈宗泉,周亚峰.曲美他嗪在不稳定型心绞痛治疗中的临床应用研究.临床和实验医学杂志[J].2009,8(3)：75-76.
[38]Chiang GG, Seflon BM. Specific dephosphorylation of the lek tyrosine protein kinase at Tyr-394 by the SHP - 1 protein-tyrosinephos - phatase[J]. J Biol Chem, 2001,276(25):23173.
[39]Bonello L Sbragia P, Amabile N, et al. Protective effect of an a. cute oral loading dose of trimetazidine on myocardial injury following percutancous coronary intervention[J]. Heart,2007,93(6):703-707.
[40]KuHday F, Ahekin E, Yazlar AS, et al. Suppression of angioplas- tymlated inflammation by pro-procedural treatment with trimetazidine[J]. Tohoku J Exp Med, 2006,208(3):203-212.
[41]Tunerir B, Colak O, Alatas O, et al. Asian measurement of trop to detect eardioprotective effect of trimetasidine during coronary artery bypass grafting[J]. Ann Thorac Surg,1999,68:2173-2176.
[42]胡怡,张银香,殷巍国产曲美他嗪治疗成人急性病毒性心肌炎疗效观察[J]中国误诊学杂志,2008,21(8)：21.
[43]DiNapoli P, DiGiovanni P, Gaeta MA, et al. Trimetazidine and reduction in mortality and hospitalization in patients with ischemic dilated cardiomyopathy:a post hoc analysis of the Villa Pinid'Abruzzo Trimetazidine Trial[J].JCardiovasc Pharmaco,l 2007,50(5):585-589.
[44]Fragasso G, Perseghin G, DeCobelli F, et al. Effects of metabolic modulation by trimetazidine on left ventricular function and phosphocreatine/adenosine triphosphateratio in patients with heart failure[J]. Eur Heart J,2006,27(8):942-948.
[45]姜淑琴.心力衰竭的中医辨治[J].现代中西医结合杂志,2004;13(13):1799.
[46]叶盈,黄飞翔,吴耀中,等.健心颗粒治疗慢性心力衰竭65例临床观察[J].中医杂志,2006；47(1)：28.
[47]张持.中医对慢性充血性心力衰蝎的认识及治疗进展[J].吉林中医药,2006;26(11)：71-72.
[48]郑军.温阳利水法治疗慢性心力衰竭48例[J].陕西中医,2005,26(2):102-103.
[49]衡冲,兰宏民,席剑.参芪葶苈大枣汤为主治疗肺心病并心力衰竭35例[J].陕西中医,2002,23(2)：105-106.
[50]李丹萍,陈强,易莉,等.益气活血法对充血性心力衰竭患者疗效和心功能的影响[J].中国中西医结合杂志,2006.26(6)：552.
[51]李庆海.吕安清,张芳,等.参麦注射液对慢性充血性心力衰竭患者心率变异性的影响[J].中国中西医结合急救杂志.2000.7(5):273—275.
[52]郑艳秋.参麦注射液杏丁注射液并用治疗心功能不全20例[J].实用中医内科志.2005,19(2)：166—167.
[53]许晓乐,季晖,谷舒怡,等.黄芪甲苷对异丙肾上腺素所致小鼠心肌肥厚的保护作用[J].中国药科大学学报,2008,38(5)：451-455.
[54]石海莲,马春来,刘燕,等.黄芪皂苷甲抑制压力过载型心肌肥厚大鼠肾素血管紧张素的过度激活[J].中国中药杂.志,2009,34(24)：3242-3245.
[55]钟匕,杜九中,于小华,等.黄芪甲甙对病毒性心肌炎细胞凋亡作用的研究[J].南华大学学报医学版,2004,32(1)：17- 19.
[56]石海莲,刘燕,马春来,等.黄芪皂苷甲对高血压大鼠离体血管舒张功能及-氧化氮的影响[J].中国新药与临床杂志,2009,28(12)：905-906.
[57]刘燕,石海莲,马春来,等.黄芪皂苷甲对高血压大鼠血管肥厚及ET-1诱导离体血管收缩功能的影响[J].中国新药与临床杂志,2009,28(11):846-r 851.
[58]刘莉,刘丰,金娟.利心Ⅰ号对60例慢性心衰患者血浆BNP水平的影响[J].中医药学报,2003,31(3),7-8.
[59]顾焕,李霁,张久亮,等.益气活血法对慢性心力衰竭病TNF-a及Ang Ⅱ的影响[J].中西医结合心脑血管病杂志,2008,6(4),381-382.
[60]刘莉,胡思南,隋艳波,等.益气温阳活血利水法对充血性心力衰竭疗效观察及其对胰岛素抵抗的影响[J].陕西中医学院学报,2013,36(1),33-36.
[61]刘莉,邹国良,索传涛.利心Ⅰ号对CH F大鼠血流动力学、心肌细胞ICAM - 1基因蛋白表达的影响[J].心脏杂志,2007,19(2),166-169.
[62]刘莉,顾焕,邹国良,等.利心Ⅰ号对充血性心力衰竭大鼠心肌细胞Bax、Bcl-2表达的影响[J].中医药信息,2006,23(1),57-59.
[63]金娟,马林沁,邹国良,等.参芪益心方对慢性心力衰竭大鼠心肌组织Caspase-3及Caspase-9蛋白表达的影响[J].世界中西医结合杂志,2014,9(2),151-155.
[64]Ingwall JS. ATP and the heart [M].MA, USA:Kluwer Academic Publish ers,2002:197-216.
[65]Wang Z, Tang X, Li Y, et al.20-Hydroxyeicosa-tetraenoic acid inhibits the apoptotic responses inpulmonary artery smooth muscle cells[J]. Eur J Pharmacol, 2008,588(1):9-17.
[66]Hugel S, Horn M, Remkes H, et al. Showing results for preservation of cardiac function and energy reserve by the angiotensin converting enzyme inhibitor quinapril during postmyocardial infarction remodeling in the rat[J]. J Cardiovasc Magn Reson, 2001,3(3):215-225.
[67]邹旭,刘泽银,林晓忠,等.暖心胶囊治疗慢性心力衰竭远期疗效及生活质量 的观察[J].中国中西医结合杂志,2006,26(3)：269—270.
[68]李绍敏.补肾法治疗充血性心衰与益气法的对比研究[J].实用中医内科杂志.2005,19(5)：480.
[69]杨帆,赖沙毅.苠苈胶囊治疗慢性心衰68例[J].中国中西医结合杂杂志2007.27(11)：1041.
[70]于忠学,关丽梅,王炎焱,等.复方黄苠无糖颗粒对心肌缺血能量代谢的影响[J].中医药信息,2003,20(1)：55.
[71]林谦,于友华.党参对冠心病心绞痛患者的血液细胞及对小鼠心肌作用的定量细胞化学观察[J].中国组织化学与细胞化学杂志,1994,3(4):398.
[72]马晨,张善飞,曹彦光,等.丹参注射液对离体大鼠心肌能量代谢的调节作用[J].中国医科大学学报,2009,40(2)：147—151.
[73]张晶,王洪新,宋莹,等.黄芪甲苷抑制大鼠心肌肥厚及改善心肌能量代谢的作用观察[J].中成药,2012,34(5)：924-928.
[74]农一兵.从补益心气与改善心肌能量代谢的关系探讨慢性心力衰竭中西医结合研究的思路[J].中医杂志,2007,48(11)：1035-1036.
[75]高想,唐艳芬,蒋凤荣,等. 利心冲剂对心衰大鼠心肌细胞能量代谢的影响[J].中华中医药杂志,2010,25(10):1686.
[76]吴伟康.四逆汤与缺血心肌的能量代谢[J].中国中医基础医学杂志,1996,2(2)：26-28.
[77]殷惠军,蒋跃绒,刘颖,等.参桂胶囊对心肌细胞能量代谢及脂质过氧化影响的研究[J].中医药信息,2004,21(3)：71-73.
[78]陈琴.心复康口服液对心梗后心衰大鼠模型心功能及心肌能量代谢干预的研究[D].北京：北京中医药大学,2008.
[79]王万铁.川芎嗪对实验性缺血再灌注损伤心肌能量代谢的干预[J].中国急救医学,2003,23(3)：129-130.
[80]黄黎华,陈渊成,程昱,等.丹参水溶性成分含量变化对大鼠离体心肌能量代谢调节的影响[J].中国药科大学学报,2011,42(4)：348-353.
[81]王承龙,缪宇,殷惠军,等.西洋参茎叶总皂苷对急性心肌梗死大鼠心肌能量代谢的影响[J].中华老年心脑血管病杂志,2005,7(5)：341-343.
[82]高卫真,康毅,娄建石,等.黄芪苷对心肌细胞氧化损伤的保护作用[J].中国 心血管杂志,2005,10(3):1661-69.
[83]Sauvanet C. Duevzin_Caubet S.di Rago JP,et al. Energetic requirements and bioenergeic modulation of mitochondrial morphology and dynamics [J]. Semnin Cell Dev Biol.2.10,21(6):558-565.
[84]Skulachev VP. Mitochondrial filaments and clusters as intracellular power-transmitting cables[J]. Trends Biochem Sci.2001,26(1):23-29.
[85]Parone PA,Da CS,Tonders D,et al.Preventing mitochondrial fission impairs mitochondrial function and leads to loss of mitochondrial DNA[J], Plos One.2008, 3(9):e3257.
[86]Hom J,Sheu SS.Morphological dynamics of mitochondria a special emphasis on cardiac muscle cells[J]. J Mol Cell Cardiol.2009,46(6):811-820.
[87]Ostuni MA, P e ranzi G, Ducroc RA, et al. Distribution, pharmacological characterization and function of the 18 kDa translocator protein in rat small intestine [J]. Biol Cell,2009,101(10):573-86.
[88]Fulvio Celsi, Paola Pizzo, Marisa Brini, et al. Mitochondria, calcium and cell death:A deadly triad in neurodegeneration[J]. Biochim Biophys Acta,2009 1787(5):335-44.
[89]Javadov S, Karmazyn M, Escobales N. Mitochondrial Permeability Transition Pore Opening as a Promising Therapeutic Target in Cardiac Diseases[J]. J Pharmacol Exp Ther, 2009,330(3):670-8.
[90]Lukyanenko V, Chikando A, Lederer WJ. Mitochondria in cardiomyocyte Ca2+ signaling[J]. Int J Biochem Cell Biol,2009,41(10):1957-71.
[91]Griffiths EJ. Mitochondrial calcium transport in the heart:Physiological and pathological roles[J]. J Mol Cell Cardiol,2009,46(6):789-803.
[92]胡胡莲美,郑文岭,朴英杰.过氧化物酶体增殖物激活受体的医学重要性[J]. 医学分子生物杂志,2005,2(2):140-142.
[93]Torra IP, Chinetti G, Duval C, et al. Peroxisome proliferators-activated receptors: from transcriptional control to clinical practice[J].Curr Opin Lipidol,2001,12: 245-254.
[94]胡琴,李隆贵.心肌脂肪酸氧化酶的基因调控机制及PPAR α的作用[J].中国病理生理杂志,2002,18(12)：1552-1555.
[95]Unger RH. Lipotoxic diseases[J]. Annu Rev Med,2002,53:319-336.
[96]Ackerman SH,Tzagologg A,Function,structure and biogenesis of mitochondrial ATP synthase[J].Prog Nudeic Acid Res Mol Biol,2005,80:94.
[97]Haynes V,Traaseth NJ,Elfering S,et al.Nitration of specific tyro-sines in F0F1 ATP synthase and activity loss in aging[J].Am J Physiol Endocrinol Metab,2010,298(5): E978.
[98]Kane LA,Youngman MJ,Jensen Re,et al.Phosphorylation of the F0F1 ATP synthase beta subunit:functional and structural consequences assessed in a model system[J] Circ Res,2010,106(3):504.
[99]Unger RH, Orci L. Lipotoxic diseases of nonadipose tissue in obesity [J].Int J Obes Relat Metab Disord,2000,24(Suppl 4):S28-S32.
[100]刘平,于宁生,雷燕,等.关于血清药理学的若干思考[J].中国中西医结合杂志,1999,10(5)：263.
[101]杨胜利,何作云,冯兵,等.缺氧/复氧诱导培养人肥大心肌细胞凋亡模型的建立[J].重庆医学,2004,33(1)：4.
[102]米永杰,李健.中药血清药理学研究概述[J].四川解剖学杂志,2006,14(4)：35-36.
[103]周明眉,杨奎,姜远平等.中药血清药理学的方法研究——反应体系中含药血清加入量的研究[J].中药药理与临床,1998,14(6)：43-44.
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