参附汤对阿霉素心脏毒性影响的实验研究
|
摘要
目的:
研究参附汤对阿霉素所致大鼠心脏毒性的生物效应,初步探讨其对阿霉素中毒心肌的保护作用。
材料与方法:
健康成年雄性SD大鼠96只,SPF级,体重220～240g,按体重随机分为7组:①空白组(N=11):常规饲养,不做任何处理;②阿霉素组(N=15):采用阿霉素(ADR)腹腔注射建立阿霉素心脏毒性模型,2.5mg/kg,每周1次,同时灌胃蒸馏水,1ml/100g,每日1次,连续用药4周;③生脉组(N=14):ADR用法同阿霉素组,同时灌胃生脉饮(等临床剂量3.5ml/kg/d),给药方案同阿霉素组;④附子空白组(N=14):用等量生理盐水代替ADR,同时灌胃附子水煎液(含生药量1.75g/kg/d),给药方案同阿霉素组;⑤附子组(N=14)、人参组(N=14)、参附组(N=14):ADR用法同阿霉素组,同时分别灌胃附子水煎液(含生药量1.75g/kg/d)、人参水煎液(含生药量0.875g/kg/d)、参附汤水煎液(含生药量2.625g/kg/d),给药方案同阿霉素组。4周后检测各组大鼠心电图及超声心动图指标;处死动物,留取一部分心肌标本做光镜与电镜检测,观察心肌组织显微结构及心肌细胞超微结构的改变;将余下心肌组织制成心肌细胞匀浆液,采用化学比色法检测大鼠心肌细胞脂质过氧化物丙二醛(MDA)的含量以及超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)的活性,初步探讨参附汤水煎液干预阿霉素心脏毒性的作用机制。
结果:
1.一般状态:参附汤能缓解阿霉素心脏毒性大鼠的症状表现,改善阿霉素心脏毒性大鼠的生存质量。
2.心脏功能:参附汤能升高阿霉素心脏毒性大鼠的QRS波群电压和,缩短Q-T间期;能抑制LVIDd与LVIDs的增大,回缩左室心腔内径,差异有统计学意义(P﹤0.05)。
3.组织形态学:参附汤能降低阿霉素心脏毒性大鼠的心脏指数;改善心肌组织空泡变性、颗粒变性、肌纤维断裂等显微结构的改变,抑制心肌细胞线粒体肿胀、嵴溶解、空泡化,肌丝断裂等超微结构的改变。
4.参附汤水煎液能提高阿霉素心脏毒性大鼠心肌细胞中的SOD及GSH-Px的活性,降低MDA的含量,差异有统计学意义(P﹤0.05)。
结论:
1.参附汤能改善阿霉素心脏毒性损伤的心脏功能。
2.参附汤能抑制阿霉素心脏毒性损伤的心肌组织结构的改变。
3.参附汤能通过抗氧化应激作用减低阿霉素心脏毒性。
Objective:
To investigate the pharmic effect of classical traditional chinese presc- riptions of Shenfu Decoction on adriamycin-induced cardiotoxicity,and to preliminary exposure its Protective Effect on Adriamycin-induced Myocardial Damage.
Material and method:
96 healthy adult male SD rats,weighing 220～240g, were randomly divided into seven groups:①control group (N=11): regular feeding, no treatment;②model group (N=15): adriamycin cardiac toxicity model was established by injecting ADR 2.5mg/kg once a week and at the same time distilled water were fed 1ml/100g once a day,continuous 4 weeks;③Shengmai group (N=14) : Adriamycin was used as the same as the model group, while ShengmaiYin (including the amount of pure liquid 3.5ml/kg/d) were fed as the same as the model group;④Monkshood control group (N=14):Equal normal saline were used instead of adriamycin, while monkshood decoction (including the amount of crude drug 1.75g/kg/d) were fed as the same as themodel group;⑤Monkshood group (N=14), ginseng group (N=14), ginseng and monkshood group (N=14): ADR were used as the same as adriamycin group. Monkshood decoction (including the amount of crude drug 1.75g/kg/d), ginseng decoction (including the amount of crude drug 0.875g/kg/d), Shenfu Decoction (including the amount of crude drug 2.625g/kg/d) were givenas the same as adriamycin group. After 4 weeks,ECG and echocardiography of rats in each group were detected;All rats were sacrificed. One part of myocardial specimens were detected by light and electron microscopy to observe microstructure and ultrastructure of myocardial tissue;The rest of myocardial specimens were made into myocardial cell homogenate. superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) of myocardial cells in rat were detected by chemical colorimetric assay to investigate mechanism of Shenfu Decoction intervented Adriamycin on cardiac toxicity.
Results:
1.General conditions: Shenfu Decoction can improve cardiac toxicity of adria- mycin and promote quality of life in rats with cardiac toxicity of adriamycin.
2. Cardiac function: Shenfu Decoction can improve QRS and shorten Q-T interval. the increase of LVIDd and LVIDs were inhibited and left ventricular cavity diameter were retracted. The difference was statistically significant (P﹤0.05).
3. Histomorphology:Shenfu Decoction can reduce cardiac index of cardiac toxicity of adriamycin.Microstructure,such as vacuolar degeneration,granular degene- ration and muscle fiber breakage etc,were improved.
Change of ultra microstructure,such as plastosome swell,mitochondrial swelling, cristae dissolution and muscle fiber breakage etc,were rehibited.
4. Shenfu Decoction can increase the SOD and GSH-Px activity of cardiac cell and lower MDA content.the difference was statistically significant(P﹤0.05).
Conclusion:
1. Shenfu Decoction can promote cardiac function of adriamycin-induced cardio- toxicity.
2. Shenfu Decoction can inhibit structure of cardiac myocyte of adriamycin- induced cardiotoxicity.
3. Shenfu Decoction can reduce toxicity of Adriamycin by anti-oxidation and anti-stress.
研究参附汤对阿霉素所致大鼠心脏毒性的生物效应,初步探讨其对阿霉素中毒心肌的保护作用。
材料与方法:
健康成年雄性SD大鼠96只,SPF级,体重220～240g,按体重随机分为7组:①空白组(N=11):常规饲养,不做任何处理;②阿霉素组(N=15):采用阿霉素(ADR)腹腔注射建立阿霉素心脏毒性模型,2.5mg/kg,每周1次,同时灌胃蒸馏水,1ml/100g,每日1次,连续用药4周;③生脉组(N=14):ADR用法同阿霉素组,同时灌胃生脉饮(等临床剂量3.5ml/kg/d),给药方案同阿霉素组;④附子空白组(N=14):用等量生理盐水代替ADR,同时灌胃附子水煎液(含生药量1.75g/kg/d),给药方案同阿霉素组;⑤附子组(N=14)、人参组(N=14)、参附组(N=14):ADR用法同阿霉素组,同时分别灌胃附子水煎液(含生药量1.75g/kg/d)、人参水煎液(含生药量0.875g/kg/d)、参附汤水煎液(含生药量2.625g/kg/d),给药方案同阿霉素组。4周后检测各组大鼠心电图及超声心动图指标;处死动物,留取一部分心肌标本做光镜与电镜检测,观察心肌组织显微结构及心肌细胞超微结构的改变;将余下心肌组织制成心肌细胞匀浆液,采用化学比色法检测大鼠心肌细胞脂质过氧化物丙二醛(MDA)的含量以及超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)的活性,初步探讨参附汤水煎液干预阿霉素心脏毒性的作用机制。
结果:
1.一般状态:参附汤能缓解阿霉素心脏毒性大鼠的症状表现,改善阿霉素心脏毒性大鼠的生存质量。
2.心脏功能:参附汤能升高阿霉素心脏毒性大鼠的QRS波群电压和,缩短Q-T间期;能抑制LVIDd与LVIDs的增大,回缩左室心腔内径,差异有统计学意义(P﹤0.05)。
3.组织形态学:参附汤能降低阿霉素心脏毒性大鼠的心脏指数;改善心肌组织空泡变性、颗粒变性、肌纤维断裂等显微结构的改变,抑制心肌细胞线粒体肿胀、嵴溶解、空泡化,肌丝断裂等超微结构的改变。
4.参附汤水煎液能提高阿霉素心脏毒性大鼠心肌细胞中的SOD及GSH-Px的活性,降低MDA的含量,差异有统计学意义(P﹤0.05)。
结论:
1.参附汤能改善阿霉素心脏毒性损伤的心脏功能。
2.参附汤能抑制阿霉素心脏毒性损伤的心肌组织结构的改变。
3.参附汤能通过抗氧化应激作用减低阿霉素心脏毒性。
Objective:
To investigate the pharmic effect of classical traditional chinese presc- riptions of Shenfu Decoction on adriamycin-induced cardiotoxicity,and to preliminary exposure its Protective Effect on Adriamycin-induced Myocardial Damage.
Material and method:
96 healthy adult male SD rats,weighing 220～240g, were randomly divided into seven groups:①control group (N=11): regular feeding, no treatment;②model group (N=15): adriamycin cardiac toxicity model was established by injecting ADR 2.5mg/kg once a week and at the same time distilled water were fed 1ml/100g once a day,continuous 4 weeks;③Shengmai group (N=14) : Adriamycin was used as the same as the model group, while ShengmaiYin (including the amount of pure liquid 3.5ml/kg/d) were fed as the same as the model group;④Monkshood control group (N=14):Equal normal saline were used instead of adriamycin, while monkshood decoction (including the amount of crude drug 1.75g/kg/d) were fed as the same as themodel group;⑤Monkshood group (N=14), ginseng group (N=14), ginseng and monkshood group (N=14): ADR were used as the same as adriamycin group. Monkshood decoction (including the amount of crude drug 1.75g/kg/d), ginseng decoction (including the amount of crude drug 0.875g/kg/d), Shenfu Decoction (including the amount of crude drug 2.625g/kg/d) were givenas the same as adriamycin group. After 4 weeks,ECG and echocardiography of rats in each group were detected;All rats were sacrificed. One part of myocardial specimens were detected by light and electron microscopy to observe microstructure and ultrastructure of myocardial tissue;The rest of myocardial specimens were made into myocardial cell homogenate. superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) of myocardial cells in rat were detected by chemical colorimetric assay to investigate mechanism of Shenfu Decoction intervented Adriamycin on cardiac toxicity.
Results:
1.General conditions: Shenfu Decoction can improve cardiac toxicity of adria- mycin and promote quality of life in rats with cardiac toxicity of adriamycin.
2. Cardiac function: Shenfu Decoction can improve QRS and shorten Q-T interval. the increase of LVIDd and LVIDs were inhibited and left ventricular cavity diameter were retracted. The difference was statistically significant (P﹤0.05).
3. Histomorphology:Shenfu Decoction can reduce cardiac index of cardiac toxicity of adriamycin.Microstructure,such as vacuolar degeneration,granular degene- ration and muscle fiber breakage etc,were improved.
Change of ultra microstructure,such as plastosome swell,mitochondrial swelling, cristae dissolution and muscle fiber breakage etc,were rehibited.
4. Shenfu Decoction can increase the SOD and GSH-Px activity of cardiac cell and lower MDA content.the difference was statistically significant(P﹤0.05).
Conclusion:
1. Shenfu Decoction can promote cardiac function of adriamycin-induced cardio- toxicity.
2. Shenfu Decoction can inhibit structure of cardiac myocyte of adriamycin- induced cardiotoxicity.
3. Shenfu Decoction can reduce toxicity of Adriamycin by anti-oxidation and anti-stress.
引文
[1] [英]希恩.C.斯威曼(Sean C Sweentamn)主编,李大魁,金有豫,等译.马丁代尔药物大典[M].北京:化学工业出版社.2008,5:517
[2]国家药典委员会编.中华人民共和国药典临床用药须知.化学药和生物制品卷[M].北京:人民卫生出版社.2005,12:638-639
[3] Lipshultz SE,Lipsitz SR,Sallan SE,et al:Long-Term Enalapril Therapy for Left Ventricular Dysfunction in Doxycycline-Treated Survivors of Childhood Cancer.J Clin Oncol.2002,20(23):4517-4522
[4]吴海鹰,管忠震.阿霉素每周给药治疗恶性肿瘤的临床观察[J].癌症.2001,20(12): 1420-1422
[5]贾国丛,宋再.乳腺癌两周方案新辅助化疗临床研究[J].肿瘤研究与临床.2006,18 (7):475-476
[6]甄永苏主编.抗肿瘤药物研究与开发[M].北京:化学工业出版社.2004,9:183.
[7] Hrushesky WJ,Bjarnason GA:Circadian cancer therapy.Journal of Clinical Oncology,1993,11:1403-1417
[8] Levi F.Chronoterapy of cancer:biological and clinical application pathol Biol,1994,42:338
[9]惠锦林.阿霉素持续输注加时辰疗法为主的CHOP方案治疗恶性淋巴瘤[J].安徽医学.2005,26(1):53-55
[10]胡欣,李光明,仁大成,等.阿霉素持续静脉注射与静脉注射给药的心脏毒性[J].实用癌症杂志.2009,24(3):306-308
[11]刘雪华.阿霉素持续静脉输注近期毒性反应观察[J].护理研究.2008, 22(3):615- 617
[12]王德兴,王刚,师自刚,等.乳腺癌肝转移介入治疗疗效评价[J].临床医学. 2003,23 (7):32
[13]徐萌主编.恶性肿瘤化疗及其对策[M].北京:军事医学出版社.2002,9:86
[14]董兰凤,赵兴茹,冯凤莲,等.阿霉素长循环热敏脂质体的研制及其靶向治疗肿瘤作用的研究[J].中国肿瘤生物治疗杂志.2005,12(1):52-56
[15]王坚成,刘晓岩,吕万良,等.新型阿霉素抗耐药性隐形脂质体的体外细胞毒和体内毒性研究[J].药学学报.2005,40(5):475-480
[16]黄海欣,李桂生,杨春旭.参芪扶正注射液治疗阿霉素引起心肌损害20例临床观察[J].右江民族医学学报.2003,25(4):552-553
[17]王晓稼,王晓婷,金琪琪.参芪扶正注射液对多柔比星致家兔心肌和免疫功能损伤的保护作用[J].实用肿瘤杂志.2005,20(4):314-315
[18]张勇,武海明,马华.生脉注射液对乳腺癌表阿霉素多程化疗心脏毒性的作用研究[J].中西医结合心脑血管病杂志.2009,7(9):1030-1031
[19]金海,孙丽敏.生脉注射液对阿霉素所致大鼠心肌线粒体损伤的影响[J].时珍国医国药.2006,17(3):329-330
[20]魏道武,李应东.生脉散对阿霉素大鼠心肌损伤的保护作用[J].中药药理与临床. 1999,15(4):9-11
[21]邹文俊,李忌,刘忠荣,等.黄芪注射液拮抗阿霉素心脏毒性作用的研究[J].中药学.2001,23(5):348-350
[22]王建智,刘庆安,王建国.黄芪注射液拮抗阿霉素致小鼠心脏毒性的作用[J].第四军医大学学报.2006,27(4):366
[23]李玉芹.黄芪注射液治疗阿霉素致乳腺癌心肌损害的临床观察[J].黑龙江医药科学.2008,31(5):37-38
[24]马飞,李小平,俞炬明,等.氧化苦参碱对阿霉素心脏毒性的影响[J].肿瘤.2007,27 (6):441-444
[25]马飞,李小平,顾建春.氧化苦参碱对兔阿霉素心肌损伤保护作用及其机制研究[J].上海交通大学学报(医学版).2009,29(6):685-688
[26]张卓然,徐长庆,韩丽萍,等.白藜芦醇对小鼠阿霉素性心肌损伤的保护作用及机制[J].中药药理学通报.2007,23(6):763-773
[27]王桂英,王永梅,张丽男,等.白藜芦醇对阿霉素致心衰大鼠心肌损伤的保护作用[J].中国中药杂志.2007,32(15):1563-1565
[28]韩锐,孙燕主编.新世纪癌的化学预防与药物治疗[M].北京:人民军医出版社. 2005,1:658
[29]裴天仙,徐长庆,李滨,等.楔皮素对阿霉素致小鼠心肌损伤的保护作用及其机制[J].药效学报.2007,42(10):1029-1033
[30]裴天仙,徐长庆,于靖,等.楔皮素抗阿霉素诱导的培养心肌细胞的凋亡[J].中药药理学通报.2008,24(4):534-538
[31]赵明奇,吴伟康,赵丹洋,等.四逆汤抗阿霉素性心力衰竭的超氧化物歧化酶机制探讨[J].中国中药杂志.2005,30(14):1111-1114
[32]包保全,张昕原,乌日娜,等.广枣总黄酮抗氧化作用的实验研究[J].中药药理与临床.2001,17(2):8-10
[33]师润,刘雳,霍杨,等.三七皂苷对阿霉素致心肌损伤保护作用的研究[J].中国中药杂志.2007,32(24):2632-2635
[34] Lefrak E A,Pitha J,Rosenheim S,et al.A Clinicopathologic analysis of adriamycin cardiotoxicity.Cancer,1973,32(2):302
[35]颜博,刘宁,国桂松,等.参附注射液对化疗中阿霉素心脏毒性的影响[J].现代中西医结合杂志.1999,8(10):1582-1583
[36]相雪梅,郭萍,闫金松.参附注射液在白血病患者阿霉素化疗中的心肌保护作用[J].中国中西医结合杂志.2004,24(8):237
[37]张薇薇,陈越,钱义明.参附注射液对含阿霉素类化疗方案减毒增效的临床观察[J].河南中医.2007,27(4):70-71
[38]吴小红,刘爱宁,蔡东炎.参附注射液对表阿霉素治疗乳腺癌毒副反应的影响[J].山东医药.2009,49(4):101-103
[39] Curtis D.Klaassen原著,黄吉武主译.毒理学:毒物的基础科学[M].人民卫生出版社.2005,9:134
[40]罗霞,李东晓,陈东辉,等.参附注射液对抗阿霉素毒性的研究[J].中药药理与临床.2000,16(5):8-9
[41]吴永涛,罗毅,顾云,等.参附注射液对大鼠心肌缺血再灌注损伤的保护作用[J].中国比较医学杂志.2007,17(1):26-29
[42]曲绍春,睢诚,于晓风,等.人参Rb组皂苷对大鼠实验性心肌缺血再灌注损伤的保护作用[J].吉林大学学报(医学版).2007,33(5):849-852
[43]周春丽,王其新.人参皂苷Rg2对体外培养低氧心肌细胞的保护作用[J].青岛大学医学院学报.2008,44(5):411-413
[44]黄先玫,康曼丽,周卸来,等.阿霉素对实验兔心肌细胞内游离钙浓度的影响[J].中国医院药学杂志.2001,21(2):73-75
[45]黄先玫,康曼丽,杜立中,等.阿霉素对实验兔心肌细胞内游离钙和肌浆网Ca2+-ATP酶活性的影响[J].浙江大学学报(医学版).2002,31(1):37-40
[46]周全乐,康亚丽,闫福曼,等.参附注射液保护阿霉素心肌毒性机理研究[J].辽宁中医药大学学报.2007,9(3):209-211
[47]闫福曼,周全乐,康亚丽,等.参附汤注射液对阿霉素致心肌细胞钙超载的影响[J].广州中医药大学学报.2008,25(4):339-342
[48]张文杰,李丽,赵春燕,等.人参皂苷单体Rb1对缺血心室肌细胞动作电位及L-型钙离子通道的影响[J].吉林大学学报(医学版).2007,33(6):978-981
[49]许浩,葛亚坤,邓同乐,等.人参皂苷Rb1对H2O2诱导新生大鼠心肌细胞凋亡的保护作用[J].中国药理学通报.2005,21(7):803-806
[50]崔东哲,陈立波,张连仲,等.人参二醇组皂苷在抗心肌缺血再灌注损伤作用中的钙拮抗剂效应[J].中国心血管杂志. 2006,11(1):1,2,31
[51]陈奇.中药药理研究方法学[M].北京:人民卫生出版社,2000,33
[52]杨建业,张迎春,唐俊明,等.阿霉素诱导大鼠心衰模型的建立[J].郧阳医学院学报.2005,24(5):269-271
[53]徐淑云主编.药理实验方法学[M].北京:人民卫生出版社,2003:1085-1086
[54]王淑琴,黄汤汀,刘巍,等.阿霉素心脏毒性160例心电图分析[J].癌症.1990,9(6): 494-496
[55] Curtis D.Klaassen原著,黄吉武主译.毒理学:毒物的基础科学[M].北京:人民卫生出版社.2005,9:543
[56]张予.阿霉素诱导的心脏毒性的机理及预防.癌症,1991,10(3):241-243
[57]陈德芳,蔡丹,谢贤和,等.阿霉素心脏毒性的表现分析[J].中国综合临床.2001,17 (5):340-341
[58]李喜明.大鼠阿霉素性心肌毒性心电图QRS波电压分析[J].中原医刊.2006,27(6): 58-59
[59]沈映君主编.中药药理学[M].北京:人民卫生出版社.2004,3,第三版:492
[60] Jae K.OH James B.Sevward A.Jamil Tajik主编.超声心动图手册(原书第3版)[M].北京:科学出版社,2009,2:127,297
[61]江德勤,田杰,白永虹,等.彩色超声心动图监测大鼠心肌病模型的建立[J].中国超声医学杂志.2005,21(8):567-569
[62]金华锋,刘芹.参附注射液治疗扩张型心肌病失代偿期22例[J].中国中西医结合杂志.2000,20(9):701-702
[63]孙文娟,刘杰,吕文伟,等.人参皂苷Rg2对犬戊巴比妥钠心力衰竭的影响[J].中国药理学通报.2003,19(6):671-674
[64]李龙,陈家.现代毒理学实验技术原理与方法[M].北京:化学工业出版社.2005,8: 311
[65]陈茂,范忠才,饶莉,等.心脏重量指数评价左心功能不全价值的研究[J].四川医学.2005,26(5):483-484
[66]薛飞,郝莉,唐波,等.参附提取物抗大鼠慢性心衰模型研究[J].中国药理与临床. 2007,23(5):41-43
[67] Francis GS.Pathophysiology of chronic heart failure.Am J Med.2001,110 Supp17A:37-46
[68] Maeda A,Honda M,Kuramochi T,et al.Doxorubicin cardiotoxicity:diastolic cardiac myocyte dysfunction as a result of imparied calcium handiing in isolated cardiac myocytes[J].Jpn Cire J.1998,62(7):505
[69]王瑛主译.肿瘤化疗与生物治疗:原理与实践[M].北京:人民卫生出版社,2008,8: 371
[70]金凯,陈中军,罗华荣.盐酸阿霉素对大鼠心肌损伤的分子机制研究[J].同济大学学报(医学版).2002,23(3):191-194
[71]吴伟康,杨辉,赵明奇,等.阿霉素性心力衰竭模型的氧化应激和凋亡机制[J].中国病理生理杂志.2004,20(8):1437-1439
[72]韩公羽,梁清华,廖耀中,等.四川江油附子新的强心成分[J].第二军医大学学报. 2007,23(5):10-13
[73]徐暾海,赵洪峰,徐雅娟,等.四川江油生附子强心成分的研究[J].中草药.2004,35 (9):964-966
[2]国家药典委员会编.中华人民共和国药典临床用药须知.化学药和生物制品卷[M].北京:人民卫生出版社.2005,12:638-639
[3] Lipshultz SE,Lipsitz SR,Sallan SE,et al:Long-Term Enalapril Therapy for Left Ventricular Dysfunction in Doxycycline-Treated Survivors of Childhood Cancer.J Clin Oncol.2002,20(23):4517-4522
[4]吴海鹰,管忠震.阿霉素每周给药治疗恶性肿瘤的临床观察[J].癌症.2001,20(12): 1420-1422
[5]贾国丛,宋再.乳腺癌两周方案新辅助化疗临床研究[J].肿瘤研究与临床.2006,18 (7):475-476
[6]甄永苏主编.抗肿瘤药物研究与开发[M].北京:化学工业出版社.2004,9:183.
[7] Hrushesky WJ,Bjarnason GA:Circadian cancer therapy.Journal of Clinical Oncology,1993,11:1403-1417
[8] Levi F.Chronoterapy of cancer:biological and clinical application pathol Biol,1994,42:338
[9]惠锦林.阿霉素持续输注加时辰疗法为主的CHOP方案治疗恶性淋巴瘤[J].安徽医学.2005,26(1):53-55
[10]胡欣,李光明,仁大成,等.阿霉素持续静脉注射与静脉注射给药的心脏毒性[J].实用癌症杂志.2009,24(3):306-308
[11]刘雪华.阿霉素持续静脉输注近期毒性反应观察[J].护理研究.2008, 22(3):615- 617
[12]王德兴,王刚,师自刚,等.乳腺癌肝转移介入治疗疗效评价[J].临床医学. 2003,23 (7):32
[13]徐萌主编.恶性肿瘤化疗及其对策[M].北京:军事医学出版社.2002,9:86
[14]董兰凤,赵兴茹,冯凤莲,等.阿霉素长循环热敏脂质体的研制及其靶向治疗肿瘤作用的研究[J].中国肿瘤生物治疗杂志.2005,12(1):52-56
[15]王坚成,刘晓岩,吕万良,等.新型阿霉素抗耐药性隐形脂质体的体外细胞毒和体内毒性研究[J].药学学报.2005,40(5):475-480
[16]黄海欣,李桂生,杨春旭.参芪扶正注射液治疗阿霉素引起心肌损害20例临床观察[J].右江民族医学学报.2003,25(4):552-553
[17]王晓稼,王晓婷,金琪琪.参芪扶正注射液对多柔比星致家兔心肌和免疫功能损伤的保护作用[J].实用肿瘤杂志.2005,20(4):314-315
[18]张勇,武海明,马华.生脉注射液对乳腺癌表阿霉素多程化疗心脏毒性的作用研究[J].中西医结合心脑血管病杂志.2009,7(9):1030-1031
[19]金海,孙丽敏.生脉注射液对阿霉素所致大鼠心肌线粒体损伤的影响[J].时珍国医国药.2006,17(3):329-330
[20]魏道武,李应东.生脉散对阿霉素大鼠心肌损伤的保护作用[J].中药药理与临床. 1999,15(4):9-11
[21]邹文俊,李忌,刘忠荣,等.黄芪注射液拮抗阿霉素心脏毒性作用的研究[J].中药学.2001,23(5):348-350
[22]王建智,刘庆安,王建国.黄芪注射液拮抗阿霉素致小鼠心脏毒性的作用[J].第四军医大学学报.2006,27(4):366
[23]李玉芹.黄芪注射液治疗阿霉素致乳腺癌心肌损害的临床观察[J].黑龙江医药科学.2008,31(5):37-38
[24]马飞,李小平,俞炬明,等.氧化苦参碱对阿霉素心脏毒性的影响[J].肿瘤.2007,27 (6):441-444
[25]马飞,李小平,顾建春.氧化苦参碱对兔阿霉素心肌损伤保护作用及其机制研究[J].上海交通大学学报(医学版).2009,29(6):685-688
[26]张卓然,徐长庆,韩丽萍,等.白藜芦醇对小鼠阿霉素性心肌损伤的保护作用及机制[J].中药药理学通报.2007,23(6):763-773
[27]王桂英,王永梅,张丽男,等.白藜芦醇对阿霉素致心衰大鼠心肌损伤的保护作用[J].中国中药杂志.2007,32(15):1563-1565
[28]韩锐,孙燕主编.新世纪癌的化学预防与药物治疗[M].北京:人民军医出版社. 2005,1:658
[29]裴天仙,徐长庆,李滨,等.楔皮素对阿霉素致小鼠心肌损伤的保护作用及其机制[J].药效学报.2007,42(10):1029-1033
[30]裴天仙,徐长庆,于靖,等.楔皮素抗阿霉素诱导的培养心肌细胞的凋亡[J].中药药理学通报.2008,24(4):534-538
[31]赵明奇,吴伟康,赵丹洋,等.四逆汤抗阿霉素性心力衰竭的超氧化物歧化酶机制探讨[J].中国中药杂志.2005,30(14):1111-1114
[32]包保全,张昕原,乌日娜,等.广枣总黄酮抗氧化作用的实验研究[J].中药药理与临床.2001,17(2):8-10
[33]师润,刘雳,霍杨,等.三七皂苷对阿霉素致心肌损伤保护作用的研究[J].中国中药杂志.2007,32(24):2632-2635
[34] Lefrak E A,Pitha J,Rosenheim S,et al.A Clinicopathologic analysis of adriamycin cardiotoxicity.Cancer,1973,32(2):302
[35]颜博,刘宁,国桂松,等.参附注射液对化疗中阿霉素心脏毒性的影响[J].现代中西医结合杂志.1999,8(10):1582-1583
[36]相雪梅,郭萍,闫金松.参附注射液在白血病患者阿霉素化疗中的心肌保护作用[J].中国中西医结合杂志.2004,24(8):237
[37]张薇薇,陈越,钱义明.参附注射液对含阿霉素类化疗方案减毒增效的临床观察[J].河南中医.2007,27(4):70-71
[38]吴小红,刘爱宁,蔡东炎.参附注射液对表阿霉素治疗乳腺癌毒副反应的影响[J].山东医药.2009,49(4):101-103
[39] Curtis D.Klaassen原著,黄吉武主译.毒理学:毒物的基础科学[M].人民卫生出版社.2005,9:134
[40]罗霞,李东晓,陈东辉,等.参附注射液对抗阿霉素毒性的研究[J].中药药理与临床.2000,16(5):8-9
[41]吴永涛,罗毅,顾云,等.参附注射液对大鼠心肌缺血再灌注损伤的保护作用[J].中国比较医学杂志.2007,17(1):26-29
[42]曲绍春,睢诚,于晓风,等.人参Rb组皂苷对大鼠实验性心肌缺血再灌注损伤的保护作用[J].吉林大学学报(医学版).2007,33(5):849-852
[43]周春丽,王其新.人参皂苷Rg2对体外培养低氧心肌细胞的保护作用[J].青岛大学医学院学报.2008,44(5):411-413
[44]黄先玫,康曼丽,周卸来,等.阿霉素对实验兔心肌细胞内游离钙浓度的影响[J].中国医院药学杂志.2001,21(2):73-75
[45]黄先玫,康曼丽,杜立中,等.阿霉素对实验兔心肌细胞内游离钙和肌浆网Ca2+-ATP酶活性的影响[J].浙江大学学报(医学版).2002,31(1):37-40
[46]周全乐,康亚丽,闫福曼,等.参附注射液保护阿霉素心肌毒性机理研究[J].辽宁中医药大学学报.2007,9(3):209-211
[47]闫福曼,周全乐,康亚丽,等.参附汤注射液对阿霉素致心肌细胞钙超载的影响[J].广州中医药大学学报.2008,25(4):339-342
[48]张文杰,李丽,赵春燕,等.人参皂苷单体Rb1对缺血心室肌细胞动作电位及L-型钙离子通道的影响[J].吉林大学学报(医学版).2007,33(6):978-981
[49]许浩,葛亚坤,邓同乐,等.人参皂苷Rb1对H2O2诱导新生大鼠心肌细胞凋亡的保护作用[J].中国药理学通报.2005,21(7):803-806
[50]崔东哲,陈立波,张连仲,等.人参二醇组皂苷在抗心肌缺血再灌注损伤作用中的钙拮抗剂效应[J].中国心血管杂志. 2006,11(1):1,2,31
[51]陈奇.中药药理研究方法学[M].北京:人民卫生出版社,2000,33
[52]杨建业,张迎春,唐俊明,等.阿霉素诱导大鼠心衰模型的建立[J].郧阳医学院学报.2005,24(5):269-271
[53]徐淑云主编.药理实验方法学[M].北京:人民卫生出版社,2003:1085-1086
[54]王淑琴,黄汤汀,刘巍,等.阿霉素心脏毒性160例心电图分析[J].癌症.1990,9(6): 494-496
[55] Curtis D.Klaassen原著,黄吉武主译.毒理学:毒物的基础科学[M].北京:人民卫生出版社.2005,9:543
[56]张予.阿霉素诱导的心脏毒性的机理及预防.癌症,1991,10(3):241-243
[57]陈德芳,蔡丹,谢贤和,等.阿霉素心脏毒性的表现分析[J].中国综合临床.2001,17 (5):340-341
[58]李喜明.大鼠阿霉素性心肌毒性心电图QRS波电压分析[J].中原医刊.2006,27(6): 58-59
[59]沈映君主编.中药药理学[M].北京:人民卫生出版社.2004,3,第三版:492
[60] Jae K.OH James B.Sevward A.Jamil Tajik主编.超声心动图手册(原书第3版)[M].北京:科学出版社,2009,2:127,297
[61]江德勤,田杰,白永虹,等.彩色超声心动图监测大鼠心肌病模型的建立[J].中国超声医学杂志.2005,21(8):567-569
[62]金华锋,刘芹.参附注射液治疗扩张型心肌病失代偿期22例[J].中国中西医结合杂志.2000,20(9):701-702
[63]孙文娟,刘杰,吕文伟,等.人参皂苷Rg2对犬戊巴比妥钠心力衰竭的影响[J].中国药理学通报.2003,19(6):671-674
[64]李龙,陈家.现代毒理学实验技术原理与方法[M].北京:化学工业出版社.2005,8: 311
[65]陈茂,范忠才,饶莉,等.心脏重量指数评价左心功能不全价值的研究[J].四川医学.2005,26(5):483-484
[66]薛飞,郝莉,唐波,等.参附提取物抗大鼠慢性心衰模型研究[J].中国药理与临床. 2007,23(5):41-43
[67] Francis GS.Pathophysiology of chronic heart failure.Am J Med.2001,110 Supp17A:37-46
[68] Maeda A,Honda M,Kuramochi T,et al.Doxorubicin cardiotoxicity:diastolic cardiac myocyte dysfunction as a result of imparied calcium handiing in isolated cardiac myocytes[J].Jpn Cire J.1998,62(7):505
[69]王瑛主译.肿瘤化疗与生物治疗:原理与实践[M].北京:人民卫生出版社,2008,8: 371
[70]金凯,陈中军,罗华荣.盐酸阿霉素对大鼠心肌损伤的分子机制研究[J].同济大学学报(医学版).2002,23(3):191-194
[71]吴伟康,杨辉,赵明奇,等.阿霉素性心力衰竭模型的氧化应激和凋亡机制[J].中国病理生理杂志.2004,20(8):1437-1439
[72]韩公羽,梁清华,廖耀中,等.四川江油附子新的强心成分[J].第二军医大学学报. 2007,23(5):10-13
[73]徐暾海,赵洪峰,徐雅娟,等.四川江油生附子强心成分的研究[J].中草药.2004,35 (9):964-966