养心通脉合剂对充血性心力衰竭大鼠干预作用的研究
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摘要
充血性心力衰竭(CHF)是大多数心血管疾病的最终归宿,临床发生率高,病死率高,是严重危害人民健康的常见疾病。也是最主要的死亡原因,随着年龄增加,发病率逐渐增高。因此,对CHF的防治已成为医学界关注的课题。
目前认为CHF是在某些基因表达下的多个环节共同参与的复杂的病理生理过程,包括神经内分泌激活、细胞凋亡、心室重构等诸多方面。传统的强心-利尿-扩血管治疗已被证明并不能完全改善病人的生活质量和预后,近年神经内分泌受体阻滞剂等治疗CHF虽然使疗效有了一定程度的提高,但仍存在耐受性差及某些不可避免的副作用等问题。当前CHF的治疗目标已从单纯改善症状向提高患者长期生活质量和降低病死率方面转变,而仅凭西药治疗仍难实现这一目标。
中医学无心力衰竭的病名,但古代中医对于心力衰竭的相关探索有着数千年的历史,相关病证及病名散见于中医古籍。历代医家通过长期的临床观察和实践认识,逐渐完善了心力衰竭的发病规律和辨证要点,总结出了丰富的临床用药经验,积累了大量的文献资料,这对防治心力衰竭是非常有益的。近年来中医药治疗CHF已积累了相当丰富的临床经验与实验研究,有较好的疗效,副作用小,安全性高,长期使用能明显改善心脏的血流动力学指标,保护心肌细胞,改善心脏能量代谢,提高患者的生活质量。因此,从中药中开发治疗CHF的有效药物具有非常重要的意义。
周仲瑛教授是我国著名中医名家,对CHF防治积累了较为丰富的经验,他认为CHF属中医学喘息、水肿、心悸、怔忡、心痹、心水等病证范畴。阴阳两虚、心脉瘀滞为其基本病机,虽阴阳俱损,但总以阳虚为主,兼有阴虚,为五脏精气虚衰、功能失调的疑难重症。在病理上虽为多系统虚损性改变,但病变重点以心肾为主;因虚致瘀是CHF血瘀证的病理特点;气虚血滞,是导致体内水液潴留的始动因素;气血阴阳之虚与瘀血、水饮之实的标本虚实之间,表现为因果错杂的转化关系。创养心通脉合剂防治CHF,取效显著。
本研究采用腹腔注射阿霉素法复制了目前公认的Wistar大鼠CHF动物模型,通过血流动力学检测,光镜、电镜观察CHF大鼠心肌细胞改变,证实模型复制成功。将动物模型分为养心通脉合剂高剂量组、中剂量组、低剂量组和卡托普利组四组进行机制研究,并设立空白组和模型组作为对照。研究结果表明养心通脉合剂具有以下作用:
1.能够改善CHF大鼠血流动力学参数,增强心肌收缩力,改善心脏舒张功能,从而改善大鼠异常的血流动力学。
2.通过抑制CHF时神经内分泌的激活,调节细胞因子,进而逆转大鼠心室重塑。
3.能够减轻CHF大鼠组织器官瘀血,降低心、肺、肝重量指数,有效改善大鼠心肌病理变化及超微结构,降低大鼠死亡率。
4.能够抑制CHF大鼠心肌组织MMP-3蛋白的表达,促进TIMP-1蛋白的表达,这可能是其抑制细胞外基质重塑,抗心肌纤维化的主要机制。
5.通过下调CHF大鼠心肌细胞Bax蛋白的表达,上调Bcl-2蛋白的表达,抑制心肌细胞凋亡,从而抑制心肌重塑。
6.具有“益阴助阳,化瘀通脉,利水消肿”功效的养心通脉合剂是治疗CHF的有效药物。该方可以从多层次、多种途径对CHF进行有效防治。
In this study, a generally accepted animal model of Wistar rats with CHF is successfully reproduced with the method of intraperitoneal injection of adriamycin. The animal model is divided into four groups for mechanism study: Yangxin Tongmai mixture of high-dose group, middle dose group, low-dose group and captopril group; blank group and model group are also established as controls. The results show that Yangxin Tongmai mixture can enhance the diastole function of myocardium and thus improve the abnormal hemodynamics of CHF rats; by inhibiting the activation of neuroendocrine and adjusting cytokines of CHF rats, Yangxin Tongmai mixture can thus reverse left ventricular remodeling in rats; it is able to reduce the blood stasis in CHF rats' tissues and organs, reduce the ponderal index of heart, lung and liver, therefore effectively improve myocardial pathologic changes and ultrastructure; it can inhibit myocardial MMP-3 protein expression, promote TIMP-1 protein expression,which is probably the main mechanism that resists myocardial fibrosis; through inhibiting myocardial Bax protein expression and promoting Bcl-2 protein expression of CHF rats, it can inhibit myocardial apoptosis. In conclusion, this prescription can carry out effective prevention and treatment of CHF from multi levels and approaches.
目前认为CHF是在某些基因表达下的多个环节共同参与的复杂的病理生理过程,包括神经内分泌激活、细胞凋亡、心室重构等诸多方面。传统的强心-利尿-扩血管治疗已被证明并不能完全改善病人的生活质量和预后,近年神经内分泌受体阻滞剂等治疗CHF虽然使疗效有了一定程度的提高,但仍存在耐受性差及某些不可避免的副作用等问题。当前CHF的治疗目标已从单纯改善症状向提高患者长期生活质量和降低病死率方面转变,而仅凭西药治疗仍难实现这一目标。
中医学无心力衰竭的病名,但古代中医对于心力衰竭的相关探索有着数千年的历史,相关病证及病名散见于中医古籍。历代医家通过长期的临床观察和实践认识,逐渐完善了心力衰竭的发病规律和辨证要点,总结出了丰富的临床用药经验,积累了大量的文献资料,这对防治心力衰竭是非常有益的。近年来中医药治疗CHF已积累了相当丰富的临床经验与实验研究,有较好的疗效,副作用小,安全性高,长期使用能明显改善心脏的血流动力学指标,保护心肌细胞,改善心脏能量代谢,提高患者的生活质量。因此,从中药中开发治疗CHF的有效药物具有非常重要的意义。
周仲瑛教授是我国著名中医名家,对CHF防治积累了较为丰富的经验,他认为CHF属中医学喘息、水肿、心悸、怔忡、心痹、心水等病证范畴。阴阳两虚、心脉瘀滞为其基本病机,虽阴阳俱损,但总以阳虚为主,兼有阴虚,为五脏精气虚衰、功能失调的疑难重症。在病理上虽为多系统虚损性改变,但病变重点以心肾为主;因虚致瘀是CHF血瘀证的病理特点;气虚血滞,是导致体内水液潴留的始动因素;气血阴阳之虚与瘀血、水饮之实的标本虚实之间,表现为因果错杂的转化关系。创养心通脉合剂防治CHF,取效显著。
本研究采用腹腔注射阿霉素法复制了目前公认的Wistar大鼠CHF动物模型,通过血流动力学检测,光镜、电镜观察CHF大鼠心肌细胞改变,证实模型复制成功。将动物模型分为养心通脉合剂高剂量组、中剂量组、低剂量组和卡托普利组四组进行机制研究,并设立空白组和模型组作为对照。研究结果表明养心通脉合剂具有以下作用:
1.能够改善CHF大鼠血流动力学参数,增强心肌收缩力,改善心脏舒张功能,从而改善大鼠异常的血流动力学。
2.通过抑制CHF时神经内分泌的激活,调节细胞因子,进而逆转大鼠心室重塑。
3.能够减轻CHF大鼠组织器官瘀血,降低心、肺、肝重量指数,有效改善大鼠心肌病理变化及超微结构,降低大鼠死亡率。
4.能够抑制CHF大鼠心肌组织MMP-3蛋白的表达,促进TIMP-1蛋白的表达,这可能是其抑制细胞外基质重塑,抗心肌纤维化的主要机制。
5.通过下调CHF大鼠心肌细胞Bax蛋白的表达,上调Bcl-2蛋白的表达,抑制心肌细胞凋亡,从而抑制心肌重塑。
6.具有“益阴助阳,化瘀通脉,利水消肿”功效的养心通脉合剂是治疗CHF的有效药物。该方可以从多层次、多种途径对CHF进行有效防治。
In this study, a generally accepted animal model of Wistar rats with CHF is successfully reproduced with the method of intraperitoneal injection of adriamycin. The animal model is divided into four groups for mechanism study: Yangxin Tongmai mixture of high-dose group, middle dose group, low-dose group and captopril group; blank group and model group are also established as controls. The results show that Yangxin Tongmai mixture can enhance the diastole function of myocardium and thus improve the abnormal hemodynamics of CHF rats; by inhibiting the activation of neuroendocrine and adjusting cytokines of CHF rats, Yangxin Tongmai mixture can thus reverse left ventricular remodeling in rats; it is able to reduce the blood stasis in CHF rats' tissues and organs, reduce the ponderal index of heart, lung and liver, therefore effectively improve myocardial pathologic changes and ultrastructure; it can inhibit myocardial MMP-3 protein expression, promote TIMP-1 protein expression,which is probably the main mechanism that resists myocardial fibrosis; through inhibiting myocardial Bax protein expression and promoting Bcl-2 protein expression of CHF rats, it can inhibit myocardial apoptosis. In conclusion, this prescription can carry out effective prevention and treatment of CHF from multi levels and approaches.
引文
[1]张琦.素问释义.科学技术文献出版社,1998.
[2]张锡纯.医学衷中参西录.河北科学技术出版社,2002.
[3]沈炎南.脉经语译.人民卫生出版社,1993.
[4]赵佶.圣济总录.人民卫生出版社,1982.
[5]巢元方.诸病源候论校释.人民卫生出版社,1983.
[6]成无己.伤寒明理论.商务印书馆,1955.
[7]张景岳.景岳全书.人民卫生出版社,1991.
[8]廖家祯,武泽民,康延培.生脉散对冠心病心绞痛患者的左心功能影响[J].中医杂志,1981,22(6):24.
[9]任树生.心脏功能与心气虚证的内在联系[J].天津中医,1985,2(2):36.
[10]文旺秀,金卓祥,严夏,等.心气虚证患者的心功能检查分析[J].实用医学杂志,1998;14(1):29-30.
[11]李十红,于英奇,李祥国,等.心虚证分型与左室舒张功能关系的研究[J].辽宁中医杂志,1997,24(3):103-104.
[12]廖家桢,王家硕,宋崇顺,等.冠心病心气虚证临床微观初探[J].上海中医杂志,1987,(11):2-6.
[13]文哲双,周江华.心阴虚证、心气虚证RAAS含量的改变及临床意义[J].湖北中医杂志,1999,21(10):445.
[14]曹雪滨,何建成,胡元会.充血性心力衰竭的中医辨证分型特点[J].甘肃中医学院学报,1999,16(3):13-16.
[15]沈金鏊.杂病源流犀火蜀[M].上海:上海科学技术出版社,1962.139.
[16]张子彬,Tsung O,张玉传.充血性心力衰竭[M].北京:科技文献出版社,2002:3:39.
[17]黄东平,罗懿明,黄衍寿,等.充血性心力衰竭中医证型及其演变规律的临床观察[J].中西医结合心脑血管病杂志,2003,12(1):685-686.
[18]吴士尧.肾上腺素能受体阻滞剂治疗慢性心力衰竭的探讨[J].国外医学,心血管疾病分册,2000,28(8):273-275
[19]黄太权,范华昌,冯青根,等.充血性心力衰竭阳虚水泛证和心气阴虚与肾上腺素及去甲肾上腺素的关系的临床观察[J].中华实用中西医杂志,2005,14(18):415
[20]杜丽,熊蔓琪,等.充血性心力衰竭少阴病阳虚水泛证的探讨[J].中国中西医结合杂志,2001,1(21):136-137.
[21]韩曼,赵小明,等.益气活血养阴方药对实验性心衰大鼠血流动力学的影响[J].陕西中医学院学报,2006,29(1):49.
[22]李绍芝,黄碧群,李球垦,等.心病气血辨证与肺功能的关系[J].中医诊断学杂志,1997,(2):62-64
[23]蒋梅先,彭鹏,唐静芬.“心肾同病”等病机与充血性心力衰竭循环激素的关系[J].上海中医药大学学报,2000,14(1):12
[24]金卓祥,文旺秀,严夏.心气虚证的动物模型实验研究新中医[J],中西医结合杂志,1998,30(2):41-42.
[25]朱伯卿,戴瑞鸿,查娟娟,等.气血相关理论的研究:补气药治疗气虚血瘀型心力衰竭[J].中西医结合杂志,1986,6(2):75.
[26]韩丽华.充血性心力衰竭刚虚证微观辨证的初步研究.河南中医药学刊[J].1996,11(2):25-28.
[27]叶增茂.活血化瘀、血小极聚集与充血性心力衰竭.中西医结合杂志[J].1984,(4):314
[28]施永德.血液流变学及其应川[M].上海第一医学院医用生物物理技术(一).1978:45-62.
[29]顾复生.充血性心力衰竭治疗进展[J].中华心血管病杂志,1993,21(6):355.
[30]皮修军,陈修.实验性心力衰竭模型的评价[J].国外医学·生理病理科学与临床分册,1987,7(3):303.
[31]皮修军,陈修.实验性心力衰竭模型的评价[J].国外医学·生理病理科学与临床分册,1987,7(3):322.
[32]黄能慧,周远鹏,刘文化.等.附子注射液和去甲基乌头碱对心血管作用的比较[J].中国药理学报,1980,(1):34.
[33]周远鹏,江京莉.附子的研究Ⅴ附子的强心有效成分之一去甲乌药碱的实验及临床研究概况[J].中药药理与临床,1992,8(3):43.
[34]王胜利,董耀荣.附子水煎液对心梗后心力衰竭大鼠血流动力学的影响[J].陕西中医,8(6):745.
[35]曹雪滨,黄河玲.人参皂甙在心血管系统药理作用研究进展[J].河北中西医结合杂志,1999,8(5):689.
[36]张杰民,陈立波,赵洪序,等.人参皂贰对心肌缺血和再灌注损伤的保护作用及浓度效应关系的实验研究[J].白求恩医科大学学报,1998,24(3):254.
[37]王健春,计国义,孙文伟,等.人参茎叶皂贰对失血性休克犬血浆皮质醇、醛固酮及单膝递质变化的影响[J].白求恩医科大学学报,1998,24(6):580.
[38]JIANG QS,HUANG XN.Inhibitory effect of ginsenoside Rbl on cardiac hypertrophy induced by monocrotaline in rat[J].Ethnopharmacol,2007,111(3):567-572.
[39]MIN JK,KIM JH,CHO YL,et al.20(S)-Ginsenoside Rg3 prevents endothelial cell apoptosis via inhibition of amitochondrial caspase pathway[J].Biochem Biophys ResCommun,2006,349(3):987-994.
[40]KANG SY,SCHINI-KERTHVB,KIMND.Ginsenosides of the protopanaxatriol group cause endothelium dependent relaxation in the rat aorta[J].Life Sci,1995,56(19):1577-1586.
[41]刘艳霞,刘在萍,焦建杰,等.黄芪营Ⅳ对正常和心功能受抑制大鼠左心室心肌力学的影响[J].中草约,2001,32(4):332-334
[42]张必祺,孙坚,胡申江,等.黄芪的内皮依赖性血管舒缩作用及机制[J].中国药理学与毒理学杂志,2005,19(1):44-48.
[43]周吉燕,樊懿,孔建龙,等.黄芪中不同提取成分对在体大鼠心肌缺血-再灌注损伤的心功能影响[J].中国中药杂志,2000,25(5):300-302
[44]彭定风,柯丽,李论,等.黄芪对缺氧心肌细胞的保护作用[J].临床心血管病杂志,2003,19(4):234-236.
[45]孟丹,陈相建,杨笛,等.黄芪总皂甙对培养心肌细胞钙超载的影响[J].中国临床康复,2004,8(3):462-463
[46]李论,柯俐,彭定凤,等.黄芪对心肌细胞缺氧的作用研究[J].中西医结合心脑血管病杂志,2003,1(2):79-80.
[47]张召才,杨英珍,李双杰,等.黄芪甲苷对病毒性心肌炎小鼠心肌纤维化的影响[J].中国新药与临床杂志,2003,22(9):519
[48]张艳.强心通脉汤治疗慢性充血性心力衰竭[J].辽宁中医杂志,1998,25(4):168
[49]扬立平.玉竹总苷对大鼠血流动力学的影晌[J].湖南中医药导报,2004,10(4):68-69.
[50]张建平.“玉竹汤”合β受体阻滞剂治疗心衰52例[J].江苏中医药.2004,25(4):23.
[51]杜锐生,李发宽,梁明达,等.三七总皂甙对体外培养乳鼠心肌细胞缺血性损伤模型的保护作用[J].中华儿科杂志,1992,30(2):74.
[52]缪丽燕,关永源,孔家均.等三七皂甙单体Rb对心肌细胞ca~(2+)内流作用的研究[J].中国药理学通报,1996,12(1):39.
[53]刘学平.三七总甙片治疗冠心病心绞痛疗效观察[J].中国中医急症,2000,9(4):147
[54]吴启端,方永奇,陈奕芝,等.石菖蒲挥发油及β细辛醚对心血管的保护作用[J].中药新药与临床药理,2005,16(5):244.
[55]王建升.石菖蒲根茎对缺血-再灌注引起大鼠心脏收缩功能障碍的作用[J],国外医药·植物药分册,2007,22(22)-77.
[56]冯亚,杜炳辉,吴作干,等行气祛痰化浊中约对血小板聚集性、红细胞变形性及血液粘度作用初探[J].福建中医学院学报,1998,8(8):24.
[57]江苏新医学院编·中药大辞典(下册)[M]·上海:上海科学技术出版社,1986-2320.
[58]吴晓玲,杨裕忠,黄东亮.葶苈子水提物对狗左心室功能的作用[J].中药材,1998,21(5):243-245
[59]甘肃省新医药学研究所.中药学[M].北京:人民卫生出版社,1982.542.
[60]刘君.泽兰的化学成分及药理研究进展[J].辽宁中医药大学学报,2008,10(1):23.
[61]郑虎占,董泽宏,佘靖,等.中药现代研究与应用[M].北京:学苑出版社,1999.2261.
[62]王本祥.现代中药药理学[M].天津:天津科学技术出版社,1997,254.
[63]Tawata M,Yoda Y,Aidak,et al.Anti-platelet section of Ca~(+2),ag-arglcoumarin derivative,purified fromG,glycyrrhiza radix planta[J]Med.1990;56(3):259
[64]潘燕.甘草水溶性总黄酮抗心肌缺血作用的研究[J].辽宁中医杂志,2004,31(2):173.
[65]郭豫涛.充血性心力衰竭的动物模型.上海实验动物科学[M].2001,20(2):122-124
[66]徐叔云.药理实验方法学[M].第2版,北京:人民卫生出版社,1994,670-672
[67]Nohl H.Identification of the site of adriamycin activation in the heart cell[J].Biochem Pharmacol,1988,37:2633.
[68]李月华.阿霉素心肌病的表现及其发病机制的探讨[J].中国约理学通报,1990,796.
[69]Kim DH,Landry AB,Lee YS.Doxorubicino induced calcium release from cardiac sarcoplaxmic reticulum vehicles[J].J Mo cell cardiol,1993,21:433
[70]Calderone A,De-ehamplain J,Rouleau JL.Adriamycin induced changes to the myocardial beta-adrenergic system in the rabbit[J].J Med cell Cardiol,1994,23:233
[7]The Digitalis Investigation Group.The effect of digoxin on mortality and morbity in patients with heart failure[J].N Engl J Med,1997,336:525-533.
[72]杨辉,吴伟康.四逆汤全方及拆方对心衰大鼠血液动力学影响的实验研究[J].新中医,2001,33(11):76
[72]毛焕元,曹林生.心脏病学[M].北京,人民卫生出版社,2001,713-720
[74]李绍芝.心气虚证研究进展[J].中国中医药信息杂志.1998,5(3):20
[75]姚冬梅.充血性心力衰竭神经内分泌的变化[J].心血管病学进展,2001,22(5):270-272
[76]Huang W,Xie C,Zhou H,et al.Association of the angiotensin-converting enzyme gene polymorpbism with chronic heart failure in Chinese Han patients[J].Eur Heart Failure,2004;6(1):23-27.
[77]Abraham MR,Olson LJ,Joyner MJ,et al.Angiotensin-converting enzyme genotype modulates pulmonary function and exercise capacity in treated patients with congestive stable heart failure[J].Circulation,2002,106(14):1794-1799.
[78]Bauersaehs J,Heek M,Fraeearollo D,et al.Addition of spironolactone to angiotensin-convelfing enzyme inhibition in heart failure improves endothelial vasomotor dysfunction:role of vascular superoxide anion folanation and endothelial nitric oxide synthase expression[J].Am Coil Cardiol,2002;39(2):351-358.
[79]陈良华,刘同宝.心力衰竭临床研究进展-心力衰竭的病理生理机制及治疗模式[J].山东医药,2005.45(13):67.
[80]孙兰军,李慧臻,赵英强,等.强心冲剂对充血性心力衰竭大鼠神经内分泌水平的影响[J].天津中医药,2003,2(4):54-56
[81]吴玉付,李醒三.肾素-血管紧张素一醛固酮系统在心血管病中的作用[J].医学文选,2005;24(6):1023-1027
[82]杜晓军.心力衰竭中心钠素的研究进展[J].心血管病学进展,1989,10(1):11-15
[83]Weber KT,Villarreal D.Aldosterone and Antialdosterone therapy in congestive heart[J].Am Cordiol,1993,71(1):3-11.
[84]Hara H,Ogihara T,Shims J,et al.Plasma atrial natriurotic peptide level as an index for the severity of congestive heart failure[J].Clin Cardiol,1987,10(5):437-442.
[85]吴华,赵华月.充血性心衰患者血浆心钠素浓度的改变和意义[J].临床心血管病杂志,1989,5(1):9-11.
[86]吴水华,蒋绮年.42例充血性心力衰竭血浆心钠索水平观察[J].临床荟荦,1993,8(8):684-685.
[87]Gottlieb SS,Kukin ML,Ahem D,et al.Prognostic importance of atrial natrluretic peptide in patients with chronic heart failure[J].Am Coil Cardiol,1989,13(12):1534-1539.
[88]吴振西,张敬礼,史芳,等.血浆心钠素与充血性心力衰竭关系探讨[J].安徽医学,1991,12(3):18-19.
[89]刘志峰,高鹏翔.复方丹参和苓桂术甘汤对缺氧所致心钠素和抗利尿激素释放的影响[J].青岛医学院学报,1996,32(2):135-136.
[90]Levine B,Kalman J,Mayer L,et al.Elevated circulating levels of tumor necrosis factor in severe chronic heart failure[J].N Zngl Med,1990,323(4):236-241.
[91]Redfield MM,Rodeheffer RJ,Jacobsen SJ,et al.Pasma brain natriuretic peptide concentration:impact of age and gender[J].Am Coil Cardial,2002,40:976.
[92]Remmen WJ,Swedberg K.European society of cardiology.Comprehensive guidelines for the diagnosis and treatment of chronic heart failure.Task force for the diagnosis and treatment of chronic heart failure of the European society of cardiology[J].Eur Heart Fail,2002,4:11.
[93]Dao Q,Krishnaswamy P,Kazanegra R,et al.Utility of B-type natriuretic peptide in the diagnosis of congestive heart failure in an urgent-care setting[J].Am Coil Cardiol,2001,37:379.
[94]Maisel AS,Krishnaswamy P,Nowak RN,et al.Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure[J].N Engl Med,2002,347(3):161.
[95]Cowie MR,Struthers AD,Wood DA,et aI.Value of natriuretic peptides in assessment of patients with possible new heart failure in primary care[J].Ancet,1999,350:1349.
[96]Tmughton RW,Frampton CM,Yandle TG,et al.Treatment of heart failure guided by plasma aminoterminal brain natriuretie peptide concentrations[J].Lancet,2000,355:1126.
[97]Yanagisawa M,Kurihara H,Kimura S,et al.A novel potent vasoconstrict or peptide produced by vascular endothelial cells[J].Nature,1988,332(6163):411-415.
[98]Toma I,Nagy A,Janosi C,et al.Effects of intrapericardially administered endothelin-lon pericardial natriuretic peptide concentrations of the insitu dog heart[J].Cardiovasc Pharmaco,2004,44:S231-233.
[99]王保和,孙兰军,赵英强,徐强.等.强心冲剂对慢性心衰大鼠内皮素的影响[J].中国中医药信息杂志,2003,11(10):29.
[100]Hare JM,Loh E,Creager MA,et al.Nitric oxide inhibits the positive inotropic response to Padrenergic stimulation in humans with leftventricular dysfunction[J].Circulation,1995,2:2198-2203.
[101]Kubota T,McTieman CF,Frye CS,et al.Dilated cardiomyopathy intransgenic mice with cardiac specific overexpression of tumor necrosis factor-alpha[J].Circ RES.1997,81:627-635.
[102]Seta Y,Shah K,et al.Basic mechanisms in heart failure:the cytokine hypothesis[J].Cardiac Failure,.1996,2:243-249.
[103]Blume A,Miller H.Role of cytokines in heart failure[J].Am Heart.1998,135(2 Pt 1):181-186
[104]王明亮.充血性充血性心力衰竭证治初探[J].山东中医杂,1995,(5):197.
[105]陈亚丽,王士昌,等.充血性心力衰竭患者血清细胞因子变化及与肾素血管紧张素系统相关性的研究[J].临床心血管病杂志,2001,17(1):26-27.
[106]Aukrust P,Veland T,Lien E,et al.Cytokine network in congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy[J].Am J cardiol,1999,83:376-382.
[107]Finkel MS,Oddis CU,Jacob TD,et al.Nevative inotropic effects of cytokines on the heart mediated by nitric oxide[J].Science,1992.257:387-389.
[108]Haque R,Karl H,Finkel MS,et al.Effects of cytokines and nitric oxide on myocardial eccouping[J].Basic Res Cardiai,1998,93:86-94.
[109]TsutanaotoT,HisanagaT,WadaA,el al.Interleukin-6 spilloverin peripheral circulation increases with the severity of heart failure,and the plasma level of interleukin-6 is an important prognostic predictor in patients with congestive heart failure[J].Am Coil Cardiol,1998,3 I(2):391-398.
[110]Lommi J,Pulkkit K.Haemodynamic neuroendocrin and metabolic correlates of circulating cytokine concentration in congestive heart failure[J].Eur Heart J,1997,18:1620-1625.
[111]Munger MA,Johnson B,Amber IJ,et al.Circulating concentrations of proinflammatory eytokines in mild or moderate heart failure secondary to isehemic or idiopathic dilated eardiomyopathy[J].Am J Cardiol,1996,77(9):723-727.
[112]张运,徐瑞.心肌纤维化-心力衰竭治疗的新靶标[J].中华医学杂志.2006,86(17):1155.
[113]Li YY,Feng YQ,Kadokami T,et al.Modulation of matrix metalloproteinase activities remodels myocardial extracellular matrix in TNF-α transgenic mice[J].Circulation,1999,100(1):1752.
[114]Tyagi SC,Kumar S,Voelker DJ,et al.Differential gene expression of extracellular matrix components in dilated cardiomyopathy[J].Cell Biochem,1996,63:185-198.
[115]王先梅.基质金属蛋白酶与左室重构[J].重庆医学,2001,3(1)32.
[116]Sharov VG,Sabbah HN,Shimoyama H,et al.Evidence of cardiocyte apoptosis in myocardium of dogs with chronic heart failure[J].Am Pathol,1996,48:141 - 149
[117]Saraste A,Viopiopulkki LM,Parvinen M,et al.Apoptosis in the heart[J].N Engl Med,1997,36:1025-1026.
[118]吴伟康.霉素性心力衰竭模型的氧化应激和凋亡机制[J].国病理生理杂志,2004,10(8):437-439.
[119]Tsujimoto,Ygerham J,Cossman J,et al,Thet(14:18),chromosome translocations involoved in B cell neo Plasms result from mistakes in VD Joining[J].Scienee,1985,229(20):1390-1393.
[120]段有文,吕刚,吴海龙,等.bcl-2和bax基因与细胞凋亡的关系及在脊髓损伤中的作用[J].中华实验外科杂志,2005,22(10):1246-1247.
[2]张锡纯.医学衷中参西录.河北科学技术出版社,2002.
[3]沈炎南.脉经语译.人民卫生出版社,1993.
[4]赵佶.圣济总录.人民卫生出版社,1982.
[5]巢元方.诸病源候论校释.人民卫生出版社,1983.
[6]成无己.伤寒明理论.商务印书馆,1955.
[7]张景岳.景岳全书.人民卫生出版社,1991.
[8]廖家祯,武泽民,康延培.生脉散对冠心病心绞痛患者的左心功能影响[J].中医杂志,1981,22(6):24.
[9]任树生.心脏功能与心气虚证的内在联系[J].天津中医,1985,2(2):36.
[10]文旺秀,金卓祥,严夏,等.心气虚证患者的心功能检查分析[J].实用医学杂志,1998;14(1):29-30.
[11]李十红,于英奇,李祥国,等.心虚证分型与左室舒张功能关系的研究[J].辽宁中医杂志,1997,24(3):103-104.
[12]廖家桢,王家硕,宋崇顺,等.冠心病心气虚证临床微观初探[J].上海中医杂志,1987,(11):2-6.
[13]文哲双,周江华.心阴虚证、心气虚证RAAS含量的改变及临床意义[J].湖北中医杂志,1999,21(10):445.
[14]曹雪滨,何建成,胡元会.充血性心力衰竭的中医辨证分型特点[J].甘肃中医学院学报,1999,16(3):13-16.
[15]沈金鏊.杂病源流犀火蜀[M].上海:上海科学技术出版社,1962.139.
[16]张子彬,Tsung O,张玉传.充血性心力衰竭[M].北京:科技文献出版社,2002:3:39.
[17]黄东平,罗懿明,黄衍寿,等.充血性心力衰竭中医证型及其演变规律的临床观察[J].中西医结合心脑血管病杂志,2003,12(1):685-686.
[18]吴士尧.肾上腺素能受体阻滞剂治疗慢性心力衰竭的探讨[J].国外医学,心血管疾病分册,2000,28(8):273-275
[19]黄太权,范华昌,冯青根,等.充血性心力衰竭阳虚水泛证和心气阴虚与肾上腺素及去甲肾上腺素的关系的临床观察[J].中华实用中西医杂志,2005,14(18):415
[20]杜丽,熊蔓琪,等.充血性心力衰竭少阴病阳虚水泛证的探讨[J].中国中西医结合杂志,2001,1(21):136-137.
[21]韩曼,赵小明,等.益气活血养阴方药对实验性心衰大鼠血流动力学的影响[J].陕西中医学院学报,2006,29(1):49.
[22]李绍芝,黄碧群,李球垦,等.心病气血辨证与肺功能的关系[J].中医诊断学杂志,1997,(2):62-64
[23]蒋梅先,彭鹏,唐静芬.“心肾同病”等病机与充血性心力衰竭循环激素的关系[J].上海中医药大学学报,2000,14(1):12
[24]金卓祥,文旺秀,严夏.心气虚证的动物模型实验研究新中医[J],中西医结合杂志,1998,30(2):41-42.
[25]朱伯卿,戴瑞鸿,查娟娟,等.气血相关理论的研究:补气药治疗气虚血瘀型心力衰竭[J].中西医结合杂志,1986,6(2):75.
[26]韩丽华.充血性心力衰竭刚虚证微观辨证的初步研究.河南中医药学刊[J].1996,11(2):25-28.
[27]叶增茂.活血化瘀、血小极聚集与充血性心力衰竭.中西医结合杂志[J].1984,(4):314
[28]施永德.血液流变学及其应川[M].上海第一医学院医用生物物理技术(一).1978:45-62.
[29]顾复生.充血性心力衰竭治疗进展[J].中华心血管病杂志,1993,21(6):355.
[30]皮修军,陈修.实验性心力衰竭模型的评价[J].国外医学·生理病理科学与临床分册,1987,7(3):303.
[31]皮修军,陈修.实验性心力衰竭模型的评价[J].国外医学·生理病理科学与临床分册,1987,7(3):322.
[32]黄能慧,周远鹏,刘文化.等.附子注射液和去甲基乌头碱对心血管作用的比较[J].中国药理学报,1980,(1):34.
[33]周远鹏,江京莉.附子的研究Ⅴ附子的强心有效成分之一去甲乌药碱的实验及临床研究概况[J].中药药理与临床,1992,8(3):43.
[34]王胜利,董耀荣.附子水煎液对心梗后心力衰竭大鼠血流动力学的影响[J].陕西中医,8(6):745.
[35]曹雪滨,黄河玲.人参皂甙在心血管系统药理作用研究进展[J].河北中西医结合杂志,1999,8(5):689.
[36]张杰民,陈立波,赵洪序,等.人参皂贰对心肌缺血和再灌注损伤的保护作用及浓度效应关系的实验研究[J].白求恩医科大学学报,1998,24(3):254.
[37]王健春,计国义,孙文伟,等.人参茎叶皂贰对失血性休克犬血浆皮质醇、醛固酮及单膝递质变化的影响[J].白求恩医科大学学报,1998,24(6):580.
[38]JIANG QS,HUANG XN.Inhibitory effect of ginsenoside Rbl on cardiac hypertrophy induced by monocrotaline in rat[J].Ethnopharmacol,2007,111(3):567-572.
[39]MIN JK,KIM JH,CHO YL,et al.20(S)-Ginsenoside Rg3 prevents endothelial cell apoptosis via inhibition of amitochondrial caspase pathway[J].Biochem Biophys ResCommun,2006,349(3):987-994.
[40]KANG SY,SCHINI-KERTHVB,KIMND.Ginsenosides of the protopanaxatriol group cause endothelium dependent relaxation in the rat aorta[J].Life Sci,1995,56(19):1577-1586.
[41]刘艳霞,刘在萍,焦建杰,等.黄芪营Ⅳ对正常和心功能受抑制大鼠左心室心肌力学的影响[J].中草约,2001,32(4):332-334
[42]张必祺,孙坚,胡申江,等.黄芪的内皮依赖性血管舒缩作用及机制[J].中国药理学与毒理学杂志,2005,19(1):44-48.
[43]周吉燕,樊懿,孔建龙,等.黄芪中不同提取成分对在体大鼠心肌缺血-再灌注损伤的心功能影响[J].中国中药杂志,2000,25(5):300-302
[44]彭定风,柯丽,李论,等.黄芪对缺氧心肌细胞的保护作用[J].临床心血管病杂志,2003,19(4):234-236.
[45]孟丹,陈相建,杨笛,等.黄芪总皂甙对培养心肌细胞钙超载的影响[J].中国临床康复,2004,8(3):462-463
[46]李论,柯俐,彭定凤,等.黄芪对心肌细胞缺氧的作用研究[J].中西医结合心脑血管病杂志,2003,1(2):79-80.
[47]张召才,杨英珍,李双杰,等.黄芪甲苷对病毒性心肌炎小鼠心肌纤维化的影响[J].中国新药与临床杂志,2003,22(9):519
[48]张艳.强心通脉汤治疗慢性充血性心力衰竭[J].辽宁中医杂志,1998,25(4):168
[49]扬立平.玉竹总苷对大鼠血流动力学的影晌[J].湖南中医药导报,2004,10(4):68-69.
[50]张建平.“玉竹汤”合β受体阻滞剂治疗心衰52例[J].江苏中医药.2004,25(4):23.
[51]杜锐生,李发宽,梁明达,等.三七总皂甙对体外培养乳鼠心肌细胞缺血性损伤模型的保护作用[J].中华儿科杂志,1992,30(2):74.
[52]缪丽燕,关永源,孔家均.等三七皂甙单体Rb对心肌细胞ca~(2+)内流作用的研究[J].中国药理学通报,1996,12(1):39.
[53]刘学平.三七总甙片治疗冠心病心绞痛疗效观察[J].中国中医急症,2000,9(4):147
[54]吴启端,方永奇,陈奕芝,等.石菖蒲挥发油及β细辛醚对心血管的保护作用[J].中药新药与临床药理,2005,16(5):244.
[55]王建升.石菖蒲根茎对缺血-再灌注引起大鼠心脏收缩功能障碍的作用[J],国外医药·植物药分册,2007,22(22)-77.
[56]冯亚,杜炳辉,吴作干,等行气祛痰化浊中约对血小板聚集性、红细胞变形性及血液粘度作用初探[J].福建中医学院学报,1998,8(8):24.
[57]江苏新医学院编·中药大辞典(下册)[M]·上海:上海科学技术出版社,1986-2320.
[58]吴晓玲,杨裕忠,黄东亮.葶苈子水提物对狗左心室功能的作用[J].中药材,1998,21(5):243-245
[59]甘肃省新医药学研究所.中药学[M].北京:人民卫生出版社,1982.542.
[60]刘君.泽兰的化学成分及药理研究进展[J].辽宁中医药大学学报,2008,10(1):23.
[61]郑虎占,董泽宏,佘靖,等.中药现代研究与应用[M].北京:学苑出版社,1999.2261.
[62]王本祥.现代中药药理学[M].天津:天津科学技术出版社,1997,254.
[63]Tawata M,Yoda Y,Aidak,et al.Anti-platelet section of Ca~(+2),ag-arglcoumarin derivative,purified fromG,glycyrrhiza radix planta[J]Med.1990;56(3):259
[64]潘燕.甘草水溶性总黄酮抗心肌缺血作用的研究[J].辽宁中医杂志,2004,31(2):173.
[65]郭豫涛.充血性心力衰竭的动物模型.上海实验动物科学[M].2001,20(2):122-124
[66]徐叔云.药理实验方法学[M].第2版,北京:人民卫生出版社,1994,670-672
[67]Nohl H.Identification of the site of adriamycin activation in the heart cell[J].Biochem Pharmacol,1988,37:2633.
[68]李月华.阿霉素心肌病的表现及其发病机制的探讨[J].中国约理学通报,1990,796.
[69]Kim DH,Landry AB,Lee YS.Doxorubicino induced calcium release from cardiac sarcoplaxmic reticulum vehicles[J].J Mo cell cardiol,1993,21:433
[70]Calderone A,De-ehamplain J,Rouleau JL.Adriamycin induced changes to the myocardial beta-adrenergic system in the rabbit[J].J Med cell Cardiol,1994,23:233
[7]The Digitalis Investigation Group.The effect of digoxin on mortality and morbity in patients with heart failure[J].N Engl J Med,1997,336:525-533.
[72]杨辉,吴伟康.四逆汤全方及拆方对心衰大鼠血液动力学影响的实验研究[J].新中医,2001,33(11):76
[72]毛焕元,曹林生.心脏病学[M].北京,人民卫生出版社,2001,713-720
[74]李绍芝.心气虚证研究进展[J].中国中医药信息杂志.1998,5(3):20
[75]姚冬梅.充血性心力衰竭神经内分泌的变化[J].心血管病学进展,2001,22(5):270-272
[76]Huang W,Xie C,Zhou H,et al.Association of the angiotensin-converting enzyme gene polymorpbism with chronic heart failure in Chinese Han patients[J].Eur Heart Failure,2004;6(1):23-27.
[77]Abraham MR,Olson LJ,Joyner MJ,et al.Angiotensin-converting enzyme genotype modulates pulmonary function and exercise capacity in treated patients with congestive stable heart failure[J].Circulation,2002,106(14):1794-1799.
[78]Bauersaehs J,Heek M,Fraeearollo D,et al.Addition of spironolactone to angiotensin-convelfing enzyme inhibition in heart failure improves endothelial vasomotor dysfunction:role of vascular superoxide anion folanation and endothelial nitric oxide synthase expression[J].Am Coil Cardiol,2002;39(2):351-358.
[79]陈良华,刘同宝.心力衰竭临床研究进展-心力衰竭的病理生理机制及治疗模式[J].山东医药,2005.45(13):67.
[80]孙兰军,李慧臻,赵英强,等.强心冲剂对充血性心力衰竭大鼠神经内分泌水平的影响[J].天津中医药,2003,2(4):54-56
[81]吴玉付,李醒三.肾素-血管紧张素一醛固酮系统在心血管病中的作用[J].医学文选,2005;24(6):1023-1027
[82]杜晓军.心力衰竭中心钠素的研究进展[J].心血管病学进展,1989,10(1):11-15
[83]Weber KT,Villarreal D.Aldosterone and Antialdosterone therapy in congestive heart[J].Am Cordiol,1993,71(1):3-11.
[84]Hara H,Ogihara T,Shims J,et al.Plasma atrial natriurotic peptide level as an index for the severity of congestive heart failure[J].Clin Cardiol,1987,10(5):437-442.
[85]吴华,赵华月.充血性心衰患者血浆心钠素浓度的改变和意义[J].临床心血管病杂志,1989,5(1):9-11.
[86]吴水华,蒋绮年.42例充血性心力衰竭血浆心钠索水平观察[J].临床荟荦,1993,8(8):684-685.
[87]Gottlieb SS,Kukin ML,Ahem D,et al.Prognostic importance of atrial natrluretic peptide in patients with chronic heart failure[J].Am Coil Cardiol,1989,13(12):1534-1539.
[88]吴振西,张敬礼,史芳,等.血浆心钠素与充血性心力衰竭关系探讨[J].安徽医学,1991,12(3):18-19.
[89]刘志峰,高鹏翔.复方丹参和苓桂术甘汤对缺氧所致心钠素和抗利尿激素释放的影响[J].青岛医学院学报,1996,32(2):135-136.
[90]Levine B,Kalman J,Mayer L,et al.Elevated circulating levels of tumor necrosis factor in severe chronic heart failure[J].N Zngl Med,1990,323(4):236-241.
[91]Redfield MM,Rodeheffer RJ,Jacobsen SJ,et al.Pasma brain natriuretic peptide concentration:impact of age and gender[J].Am Coil Cardial,2002,40:976.
[92]Remmen WJ,Swedberg K.European society of cardiology.Comprehensive guidelines for the diagnosis and treatment of chronic heart failure.Task force for the diagnosis and treatment of chronic heart failure of the European society of cardiology[J].Eur Heart Fail,2002,4:11.
[93]Dao Q,Krishnaswamy P,Kazanegra R,et al.Utility of B-type natriuretic peptide in the diagnosis of congestive heart failure in an urgent-care setting[J].Am Coil Cardiol,2001,37:379.
[94]Maisel AS,Krishnaswamy P,Nowak RN,et al.Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure[J].N Engl Med,2002,347(3):161.
[95]Cowie MR,Struthers AD,Wood DA,et aI.Value of natriuretic peptides in assessment of patients with possible new heart failure in primary care[J].Ancet,1999,350:1349.
[96]Tmughton RW,Frampton CM,Yandle TG,et al.Treatment of heart failure guided by plasma aminoterminal brain natriuretie peptide concentrations[J].Lancet,2000,355:1126.
[97]Yanagisawa M,Kurihara H,Kimura S,et al.A novel potent vasoconstrict or peptide produced by vascular endothelial cells[J].Nature,1988,332(6163):411-415.
[98]Toma I,Nagy A,Janosi C,et al.Effects of intrapericardially administered endothelin-lon pericardial natriuretic peptide concentrations of the insitu dog heart[J].Cardiovasc Pharmaco,2004,44:S231-233.
[99]王保和,孙兰军,赵英强,徐强.等.强心冲剂对慢性心衰大鼠内皮素的影响[J].中国中医药信息杂志,2003,11(10):29.
[100]Hare JM,Loh E,Creager MA,et al.Nitric oxide inhibits the positive inotropic response to Padrenergic stimulation in humans with leftventricular dysfunction[J].Circulation,1995,2:2198-2203.
[101]Kubota T,McTieman CF,Frye CS,et al.Dilated cardiomyopathy intransgenic mice with cardiac specific overexpression of tumor necrosis factor-alpha[J].Circ RES.1997,81:627-635.
[102]Seta Y,Shah K,et al.Basic mechanisms in heart failure:the cytokine hypothesis[J].Cardiac Failure,.1996,2:243-249.
[103]Blume A,Miller H.Role of cytokines in heart failure[J].Am Heart.1998,135(2 Pt 1):181-186
[104]王明亮.充血性充血性心力衰竭证治初探[J].山东中医杂,1995,(5):197.
[105]陈亚丽,王士昌,等.充血性心力衰竭患者血清细胞因子变化及与肾素血管紧张素系统相关性的研究[J].临床心血管病杂志,2001,17(1):26-27.
[106]Aukrust P,Veland T,Lien E,et al.Cytokine network in congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy[J].Am J cardiol,1999,83:376-382.
[107]Finkel MS,Oddis CU,Jacob TD,et al.Nevative inotropic effects of cytokines on the heart mediated by nitric oxide[J].Science,1992.257:387-389.
[108]Haque R,Karl H,Finkel MS,et al.Effects of cytokines and nitric oxide on myocardial eccouping[J].Basic Res Cardiai,1998,93:86-94.
[109]TsutanaotoT,HisanagaT,WadaA,el al.Interleukin-6 spilloverin peripheral circulation increases with the severity of heart failure,and the plasma level of interleukin-6 is an important prognostic predictor in patients with congestive heart failure[J].Am Coil Cardiol,1998,3 I(2):391-398.
[110]Lommi J,Pulkkit K.Haemodynamic neuroendocrin and metabolic correlates of circulating cytokine concentration in congestive heart failure[J].Eur Heart J,1997,18:1620-1625.
[111]Munger MA,Johnson B,Amber IJ,et al.Circulating concentrations of proinflammatory eytokines in mild or moderate heart failure secondary to isehemic or idiopathic dilated eardiomyopathy[J].Am J Cardiol,1996,77(9):723-727.
[112]张运,徐瑞.心肌纤维化-心力衰竭治疗的新靶标[J].中华医学杂志.2006,86(17):1155.
[113]Li YY,Feng YQ,Kadokami T,et al.Modulation of matrix metalloproteinase activities remodels myocardial extracellular matrix in TNF-α transgenic mice[J].Circulation,1999,100(1):1752.
[114]Tyagi SC,Kumar S,Voelker DJ,et al.Differential gene expression of extracellular matrix components in dilated cardiomyopathy[J].Cell Biochem,1996,63:185-198.
[115]王先梅.基质金属蛋白酶与左室重构[J].重庆医学,2001,3(1)32.
[116]Sharov VG,Sabbah HN,Shimoyama H,et al.Evidence of cardiocyte apoptosis in myocardium of dogs with chronic heart failure[J].Am Pathol,1996,48:141 - 149
[117]Saraste A,Viopiopulkki LM,Parvinen M,et al.Apoptosis in the heart[J].N Engl Med,1997,36:1025-1026.
[118]吴伟康.霉素性心力衰竭模型的氧化应激和凋亡机制[J].国病理生理杂志,2004,10(8):437-439.
[119]Tsujimoto,Ygerham J,Cossman J,et al,Thet(14:18),chromosome translocations involoved in B cell neo Plasms result from mistakes in VD Joining[J].Scienee,1985,229(20):1390-1393.
[120]段有文,吕刚,吴海龙,等.bcl-2和bax基因与细胞凋亡的关系及在脊髓损伤中的作用[J].中华实验外科杂志,2005,22(10):1246-1247.