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三七苦碟子提取物抗大鼠实验性心肌缺血作用及机制的研究
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摘要
目的:利用生理学、生物化学、病理形态学及分子生物学等技术,探讨三七苦碟子提取物抗心肌缺血的作用及其机制。
     方法:健康雄性Wistar大鼠分成空白组、模型组、SK治疗组(灌服三七和苦碟子提取物自制剂)高、中、低剂量组、阳性对照组(灌服复方丹参滴丸);采用异丙肾上腺素一次性多点皮下注射,复制大鼠心肌缺血动物模型。通过生理(心电图)及生化法(血清酶学),观测三七苦碟子提取物抗心肌缺血的作用。运用光镜、电镜,观察三七苦碟子提取物对缺血大鼠心肌损伤及细胞凋亡的影响,并运用免疫组化、蛋白印记法观察其对细胞凋亡相关基因Bcl-2、Caspase-3蛋白表达的影响研究,探讨三七苦碟子提取物抗心肌缺血作用的机制。
     结果:
     1.三七苦碟子提取物对急性心肌缺血大鼠的心电图S-T段、血清磷酸肌酸激酶(CK)、磷酸肌酸激酶同功酶(CK-MB)相关指标均有较好的调节效果,且呈量效依赖关系,其中尤以SK高、中剂量组为显著,其总体作用优于阳性对照组(复方丹参滴丸)。
     2.在研究中,我们发现三七苦碟子提取物能够显著降低急性心肌缺血大鼠血清CK、CK-MB水平,提示三七苦碟子提取物可使血管扩张,减轻心肌缺血损伤。
     3.在研究中,我们发现三七苦碟子提取物能使急性心肌缺血大鼠受损心肌组织的显微结构和超微结构明显得到改善,其中尤以SK高、中剂量组为显著,其总体作用优于阳性对照组(复方丹参滴丸)。提示三七苦碟子提取物可减轻心肌缺血损伤,对心肌细胞有保护作用。
     4.三七苦碟子提取物能分别增加和抑制Bcl-2、Caspase-3基因的蛋白表达,抑制和阻断急性心肌缺血大鼠心肌细胞过度凋亡的发生,其高、中剂量组的作用均优于阳性对照组(复方丹参滴丸)。
     结论:三七苦碟子提取物能有效的抗大鼠急性心肌缺血。其作用机制可能与降低急性心肌缺血大鼠血清CK、CK-MB水平、抑制心肌细胞凋亡,以及调节心肌Bcl-2、Caspase-3等凋亡相关蛋白表达密切相关,通过多种综合的作用机制起到保护心肌细胞、抗急性心肌缺血损伤的作用。
Background:Extract fromlxeris of Panax notoginseng and Ixeris sonchifolia-hance (SK) is an effective durg that be summed up by my tutor.The principle of supplementing qi and activating blood is the therapeutiec prineiple Which treating CHD(coronary heart disease) of asthenic qi and blood stasis.In this treatise,through animal experiments studies,we can see themechanisms of how Extract SK can play an influential role in prevention and treatment of CHD can be deeply probed into.
     objectives:To observe the effect of traditional Chinese medieinal herb(SK) on acute myocardial ischemia modle rats,and to approach the action and mechanism of preventing coronary heart disease(CHD).
     Method:Using modern scientific technology to study SK,including pharmacy, pharmacology and phathology.Using danshendiwan positive control and acute myocardial ischemia modle rats as study object,we can observe the effect of different concentration SK on ECG,and BL00D VISCOSITY,CK,CK-MB,as well the adjustment of Bcl-2,Caspase-3 gene and apoptosis by test methods such as enzyme assay,opties microscope,electric microscope,morphologic nitrate reduction,immunohisto-chemical method,western bioting.
     Results:
     1 SK has obvious dose-dependent decrease effect on model rats S-T segment deviation, CK,CK-MB,and the effect is better than danshendiwan when middle and high dosage.
     2 The studies show that SK infusion manifest the anti-damage function to acute myocardial ischemia;SK has obvious regulation effect on model rats;it can debase CK, CK-MB.
     3 The studies show that SK infusion manifest the anti-damage function to acute myocardial ischemia and can protect cardiac muscle cell;SK has obvious improvement effect to micro-structure of showing and ultra micro-structure on model rats;it can debase cardiac muscle organize.and the effect is better than Danshendiwan when middle and high dosage.
     4 SK infusion may increase or disrupt the porceduer of cell apoptosis by regulating the expression of Bcl-2 gene and Caspase-3 gene,depress or disrupt the over-apoptosis procedure of acute myocardial cells,and the effect is better than Danshendiwan when middle and high dosage.
     Conclusions:SK have effective anti-myocadrial ischemia function.The mechanism probably relate to inhibiting CK,CK-MB secretion,and depress or disrupt the procedure of cell apoptosis by regulating the expression of Caspase-3 and Bcl-2 gene.The search results shown above suggest that SK can protect cardiac muscle cell and play a significant anti-damage role to myocardial ischemia thorugh a mlltiplechannelled synthetically mechanism.
引文
[1]马月静.中医药治疗冠心病及其心绞痛研究进展[J].中国药房,2005,16(21):1665-1667.
    [2]Sylvia P.Ginkgo biloba extract pretreatment limits free radicalsoxidative stress in patients under going coronary by passsurgery[J].Cardiovas Drugs Therapy,1997,11(2):121-126.
    [3]姜建萍.银杏的现代药理研究概况[J].中国中医药科技,2000,7(4):268-269.
    [4]张卫东,陈万生,孔德云,等.灯盏细辛化学成分的研究[J].中国药学杂志,2000,35(8):54-57.
    [5]张松,沈祥春,徐立,等.注射用灯盏花素对麻醉犬急性心肌缺血的影响[J].中药药理与临床,2004,20(2):13-1442.
    [6]李万玉,徐晓玉.李法琪.等.灯盏花素对高血压大鼠血小板内游离钙浓度和聚集率及心脏重塑的影响[J].中国新药杂志,2004.13(3):220-223.
    [7]黄秀兰,王伟,周亚伟.淫羊藿总黄酮注射液对冠脉结扎致大鼠心肌缺血的保护作用[J].中国中西医结合杂志,2006,26(1):68-71.
    [8]黄秀兰,王伟,周亚伟.淫羊藿总黄酮注射液对冠脉结扎致犬实验性心肌梗死的治疗作用[J].中国药学杂志,2006,41(3):185-188.
    [9]黄秀兰,张雪静,王伟,等.淫羊藿总黄酮注射液对垂体后叶素致大鼠心肌缺血的保护作用[J].中华中医药杂志,2005,20(90):533-534.
    [10]黄秀兰,王伟,周亚伟.淫羊藿总黄酮注射液对正常麻醉开胸犬血流动力学的影响[J].解放军药学学报,2006,22(1):65-69.
    [11]张秀芹,候金玲,朱燕,等.葛根素葡萄糖注射液对犬实验性心肌缺血的影响[J].中国新药杂志,2001,10(4):272-274.
    [12]朱庆磊,吕欣然.葛根素的药理学和临床应用研究进展[J].中草药,1997,28(11):693-697.
    [13]Packer L.Antioxidant activity and biologic properties of aprocyanidin-rich extract from pinebark,pycnogenol[J].Free Radical BiolMed,1999,27(5/6):704-711.
    [14]冯国清,秦晓晨,刘洁,等.黄芪对大鼠心肌缺血再灌注损伤的防护作用[J].中药药理与临床,1997,13(3):27-29.
    [15]张曦,李宏,侯茂君,等.黄芩及其有效成分的药理学研究进展[J].天津药学,2000,12(4):8-11
    [16]张喜平,例宗芳,刘效恭.黄芩素的药理研究概况[J].中国药理学通报,2001,17(6):711-713.
    [17]黄伟晖,宋纯清.当归的化学和药理研究进展[J].中国中药杂志,2001,26(3):147-151,155.
    [18]李俊峰,李文军.绞股蓝药理作用研究进展[J].河北中医药学报,1999,14(2):23-24.
    [19]张灼,陈立新,秦腊梅,等.黄芪皂苷对大鼠心肌缺血-再灌注损伤血流动力学和氧自由基的影响[J].中国中医药信息杂志,2000,7(3):7.
    [20]Shen XT,Zhou SP,Liu XJ.HuangQi.(Astargalus membranaceus)constituents with positive inotropic activity[J].Aeta Phamr Sinica,1993,14(1):94.
    [21]唐旭东,姜建青.姜大春,等.三七总皂苷对心肌缺血-再灌注中中性粒细胞核因子-κB活化及其粘附的影响[J].中国药理学通报,2002,18(5):556-559.
    [22]宋晓亮,高广猷,叶丽虹.山麦冬总皂苷对实验性心肌缺血的影响[J].中国药理学通报,1996,12(4):329-332
    [23]孔乾,睢大员,于晓风,等.人参Rb组皂苷对实验性心肌梗死犬心脏血流动力学和氧代谢的影响[J].中草药,2002,33(8):718-722.
    [24]于晓风,曲绍春,徐华丽,等.人参果皂苷对大鼠实验性心肌梗死的保护作用[J].吉林大学学报(医学版),2003,29(5):573-576.
    [25]金有豫,耿朝晖.知母皂甙D对心肌缺血/复灌性损伤的保护作用的分析[J].首都医学院学报,1994,15(2):138-140.
    [26]易进海.麦冬研究进展[J].华西药学杂志,1993,8(1):32-33.
    [27]王博文,马隆恩,刘同库,等.蒺藜皂甙治疗冠心病心绞痛406例临床观察[J].中西医结合杂志,1990,10(2):85.
    [28]李琳,孙莉莎,徐江平.丹酚酸B对犬心肌梗死的治疗作用[J].中成药,2004,26(3):215-218.
    [29]吴万征.丹参素研究概况[J].广东微量元素科学,2001,8(3):17-19.
    [30]章常华,许东晖,梅雪婷,等.抗心肌缺血天然产物研究进展[J].中药材,2003,26(40):288-293.
    [31]DAI De Zai,CHEN Shi Hong,FENG Yu.Tea polyphenols and quercetinpreventing the heart,brain and liver from the injury by free radicals incomparison with ascorbic acid[J].Chin J Nat Med,2004,2(4):223-231.
    [32]李立中.茶多酚对大鼠心肌缺血再灌注损伤的影响[J].中药药理与临床,1997,13(4):21-22.
    [33]闵清,白育庭,舒思洁,等.延胡索乙素对异丙肾上腺素所致心肌坏死的保护作用[J].中医药学报,2001,29(4):44-45.
    [34]邱蓉丽,李祥,陈建伟,等.延胡索总生物碱抗心肌缺血作用的实验研究[J].中国中医药科技,2001,8(4):265
    [35]郭治彬,付金国.小檗胺的心血管药理作用研究进展[J].中国中西结合杂志,2005,25(8):765-768
    [36]段红,李源,王华平,等.川芎嗪对缺血再灌注大鼠心肌细胞凋亡的影响[J].武警医学,2000,11(2):20-22.
    [37]李源,段红,王天成,等.川芎嗪对再灌注大鼠心肌细胞C-fos基因表达的影响[J].心脏杂志,2000,12(3):213-215.
    [38]王小晨,黄继汉,李见春,等.环维黄杨星D对实验性心脏损害的保护作用[J].中国临床药理学与治疗学,2003,8(1):63-65.
    [39]梁秉文,张朝位.黄杨宁.中药与心脑血管疾病[M].北京:蓝天出版社.2000,44
    [40]周玖瑶.环维黄杨星D药理研究概况[J].广州中医药大学学报,2005,22(1):70-74.
    [41]赵阳,马百平,王升启,等.中药所含甾体皂苷与三萜皂苷防治心血管疾病的研究进展[J].中国药学杂志,2003,28(1):3-7.
    [42]Lee,YM,Hsiao G,Chen HR,et al.Magmlol redLCes myocarrlial ischemia reperfision injuy via neurophil inhihitiorin rats CX[J].hamracol,2001,422(1-3):159-167.
    [43]包保全,张昕原,巴根那,等.心肌细胞培养技术的建立及蒙药广枣总黄酮对培养心肌细胞的抗氧化作用[J].内蒙古民族大学学报(自然科学版),2001,16(1):85-87.
    [44]柯于鹤.丹参对乳鼠心肌细胞凋亡的影响[J].山东中医药大学学报,2001,25(5):376-378.
    [45]罗伟,程晓曙,吴清华,等.人参总皂甙对心肌缺血电生理与心肌细胞凋亡影响的实验研究[J].江西医药,2002,37(1):20-23.
    [46]金劲松,高鸣,马琼英.黄芪对MMS损伤乳鼠心肌细胞影响的实验研究[J].中国中西医结合肾病杂志,2002,3(1):16-17.
    [47]陈图刚,罗伟,程晓曙,等.人参总皂苷对心肌细胞缺血再灌注损伤的保护作用[J].江西医学院学报,2001,41(1):10-12.
    [48]刘晓春,刘正湘,施静,等.人参对缺血再灌注大鼠心肌细胞凋亡影响的实验研究[J].中国组织化学与细胞化学杂志,2000,9(3):261-263.
    [49]常志文,刘琦.缺血再灌注心肌细胞凋亡及药物干预[J].中国新药杂志,2000,9(1):28-30.
    [50]马世玉,吴基良,陈金和,等.倒卵叶五加总皂甙对大鼠心肌缺血/再灌注损伤后细胞凋亡的作用及机制[J].中国心血管杂志,2003,8(1):15-17,24.
    [51]马世玉,向继洲,吴基良,等.倒卵叶五加总皂甙对大鼠心肌缺血再灌注损伤后c-fos mRNA表达的影响[J].临床心血管病杂志,2003.19(1):36-38.
    [52]常天辉,刘晓阳,章新华,等.白花前胡及前胡甲素对心肌缺血再灌注大鼠IL-6及Fas、bax、bcl-2蛋白表达的影响[J].中国医科大学学报,2003,32(1):1-3,6.
    [53]李庆林,桂新,陈志武,等.金丝桃苷抑制大鼠心肌缺血再灌注损伤引起的细胞凋亡作用的机制[J].药学学报,2002,37(11):849-852.
    [54]周梅花,何建新,俞宙.冬虫夏草水提液体外对缺氧再给氧时心肌细胞脂质过氧化作用的影响[J].广东药学,1998,2:43-44.
    [55]夏腊梅,伍杰雄.川芎嗪对大鼠心肌线粒体损伤的保护作用[J].中国药房,2002,13(7):400-401.
    [56]程虹,王芳,刘惟莞.姜黄素对培养乳鼠心肌细胞损伤的抗氧化作用[J].广东药学院学报,2005,21(6):703-705.
    [57]夏腊梅,伍杰雄.川芎嗪对心肌细胞核钙转运功能异常的保护[J].中国临床药理学与治疗学,2002,7(2):124-126.
    [58]崔东哲,陈立波,张连仲,等.人参二醇组皂甙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.
    [59]陈少如,陈穗,郑鸿翱,等.益母草治疗心肌缺血或再灌注损伤及其机制研究[J].微循环学杂志,2001,11(4):16-19.
    [60]HAN Dong Yun,LI Jin Ming,YANG Xue Ying,et al.Effects of N2methylberbamine on transient outward potassium current and delayed rectifierpotassium current in human atrial myocytes[J].Chin J Pharmacol Toxicol,2003,17(5):350-353.
    [61]黄启壬,曹守仪,万福生,等.油茶皂甙对缺血大鼠心肌线粒体Na~+、Ca~(2+)、Mg~(2+)含量及ATP酶活性的影响[J].中国临床药理学与治疗学杂志,1999,4(3):195-197.
    [62]张川,袁高辉,韦凡平.血清肌钙蛋白I在急性心肌梗死中的诊断价值[J].现代中西医结合杂志,2006,15(5):557-558.
    [63]梁铁军,高顺宗,王爱武,复方丹参滴丸对急性心肌梗塞病人血清肌钙蛋白T影响[J].时珍国医国药,1999,10(2):90.
    [64]吴波,陈思维,曹虹,等.薤白提取物对心肌缺氧缺血及缺血再灌注心肌损伤的保护作用[J].沈阳药科大学学报,2001,18(2):131-133.
    [65]司秋菊,王亚利,王鑫国,等.蜈蚣有效成分抗心肌缺血作用的研究[J].河北中医药学报,2001,16(2):1-3.
    [66]祝晨,刘中秋,刘良.革叶猕猴桃果实不同提取部位抗心肌缺血作用的比较研究[J].中药药理与临床,2001,17(1):19-21.
    [67]新华·那比,艾尼瓦尔,周承明,等.赤土茯苓菅对离体大鼠心脏缺血再灌注损伤的保护作用[J].西北药学杂志,2000,15(3):110-112.
    [68]邵春红,新华,周承明,等.赤土茯苓苷对大鼠心肌缺血的保护作用[J].新疆医科大学学报,2000,23(3):205-207.
    [69]Lee,YM,Hsiao G,Chen HR,et al.Magnolol reduces my-ocardial ischemia/reperfusion injury via neurophil inhibitionin rats[J].Eur J Pharmacol,2001,422(1-3):159-167.
    [70]尹虹,薛存宽,叶建明,等.缬草提取物抗心肌缺血再灌注损伤的实验研究[J].微循环学杂志,2000,101(1):12-14.
    [71]李海聪,张卫军,木拉迪,玉赛音,等.大蒜素对急性心肌缺血兔血浆内皮素和一氧化氮的影响[J].中医杂志,2001,42(5):302-303.
    [72]叶开和,任先达,熊爱华,等.飞龙掌血水提物对心肌缺血兔心功能和血液动力学的影响[J].中国病理生理杂志,2000,16(7):606-609.
    [73]周华东,李敬诚,主编.脑血管疾病基础与临床进展[M].重庆大学出版社出版,1998,12:280-286.
    [74]钱方庆.川芎嗪注射液的临床新用[J].中医药信息,1997,14(5):13-14.
    [75]陈新谦,金有豫,主编.新编临床药物学[M].人民卫生出版社,1998,14:268-271.
    [76]冯津萍,卢奕,赵炳让,等.黄芪抑制家兔心肌缺血-再灌注时细胞凋亡的实验研究 [J].中国中西医结合急救杂志,2001,8(1):13-15.
    [77]梁明,韩竹梅.黄芪冻干粉对实验性心肌缺血大鼠心电图的影响[J].中医药信息,2000,17(1):54-55.
    [78]尹俊,王鸿利.益母草对心肌缺血大鼠血液流变学及血栓形成的影响[J].血栓与止血学,2001,(1):13-15.
    [79]刘宗莲,高淑英.复方丹参滴丸治疗冠心病心绞痛的疗效分析[J].中成药,1997,19(7):20-21.
    [80]尹翠梅,赵瑞芳.黄芪注射液加普乐林注射液治疗糖尿病冠心病心绞痛的疗效观察[J].中国中药杂志,1997,22(5):312-314.
    [81]郭自强.党参加丹参对冠心病心绞痛患者血小板功能以及血浆TXA2和PGI2含量的影响[J].北京中医学院学报,1992,(1):36-38.
    [82]孙敬昌,曲京峰.附子白芍配伍的理论探讨及对心肌缺血动物作用的初步观察[J].山东中医药大学学报.2000,24(3):209-214.
    [83]唐铁军,吴伟康,卢汉平,等.四逆汤调节大鼠缺血心肌β受体信号转导的机制[J].中国中西医结合杂志,2001,21(3):206-208.
    [84]杨辉,吴伟康,陈建萍,等.保心胶囊对实验性犬心肌缺血血流动力学的影响[J].中国病理生理杂志,2000,16(3):218-221.
    [85]葛金文,陈大舜,刘健华,等.王清任三逐瘀汤抗家兔心肌缺血损伤作用的比较研究[J].中国中医基础医学杂志,2000,(2):37-41.
    [86]葛金文,陈大舜,朱惠斌,等.王清任三逐瘀汤对心肌缺血家兔凝血及纤溶功能的影响[J].中国中医药信息杂志,2000,7(1):22-24.
    [87]高承贤,丁志山,沃兴德,等.血府逐瘀汤抗心肌缺血及耐缺氧作用的实验研究[J].浙江中医学院学报,2001,25(2):45-46.
    [88]吴波,陈思维,王敏伟,等.瓜蒌薤白白酒汤提取物抗心肌缺血缺氧及最佳处方的筛选[J].中草药,2000,31(11):844-845.
    [89]程秀娟,王乃利,吴波,等.瓜蒌薤白白酒汤抗心肌缺氧缺血处方优选[J].沈阳药科大学学报,2000,17(5):375-377.
    [90]杜智敏,邱晓红,李宝馨,等.冠心胶囊对大鼠心肌缺血的保护作用[J].中国药学杂志,2000,35(10):664-667.
    [91]李全风,王孝铭,朱世军,等.复方丹参滴丸对缺氧心肌细胞内钙离子平均荧光强 度的影响[J].中国病理生理杂志,2001,17(7):690-691.
    [92]马静,王宗仁,马世平,等.降粘抗栓片对犬冠状动脉血流量及阻力的影响[J].西安医科大学学报,2001,2(3):221-223.
    [93]王晓岚,周次清.心痛宁对大鼠血小板聚集及膜流动性的影响[J].中国血液流变学杂志,2001,1(2):102-104.
    [94]韩玲,陈可冀.益心康胶囊对整体及离体大鼠心肌肌纤维膜损伤的保护作用[J].中国中医药信息杂志,2001,8(4):38-40.
    [95]韩玲,陈可冀.益心康胶囊体外自由基清除作用及对线粒体质子跨膜转运的影响[J].中国中医药科技,2001,8(3):147-149.
    [96]韩玲,任建平,杨素娟,等.益心康胶囊与复方丹参片心血管保护作用的比较研究[J].中国中医结合急救杂志,2001,8(1):9-12.
    [97]张赛英,陈大舜,王行宽.心痛灵对心肌缺血大鼠血清酶、内皮素及降钙素基因相关肽等的影响[J].湖南中医学院学报.2000,20(2):12-13.
    [98]江苏新医学院.中药大辞典(上册)[M].上海:上海人民出版社.1975.1300-1301.
    [99]Ma Jiyuan,Wang Zheng tao.Sesquiterpene lactones from Ixeris sonchifolia[J].Phyto chemistry,1998,48(1):201.
    [100]Feng XZ,Dong M,Gao ZJ,et al.Three new tfiterpenoidsaponins from Ixeris sonchifolia and their cytotoxic activity[J].Planta Med,2003,69(11):1036.
    [101]封锡志,徐绥旭,李文,等.苦碟子中的新黄酮苷(Ⅱ)[J].中国药物化学杂志,2000,10(2):143.
    [102]Lu J,Feng X,Sun Q,et al.Efect of six flavonoid corn-pounds from hefts sonchifolia on stimuhs-induced superoxide generation and tyrosyl phosphorylation in human neu-trophils[J].Clin Chim Aaa,2002,316(1-2):95.
    [103]封锡志.抱茎苦荬菜的化学成分和生物活性研究[D].沈阳:沈阳药科大学博士学位论文,2001,6.
    [104]王敏杰,王金兰,张树军.苦碟子根部化学成分研究[J].齐齐哈尔大学学报,2005,21(4):4-5、9.
    [105]Kim Jai-Young,Oh Se-won,Koh Jin-Bog.Efectsofgodulbaegi power on gowth,protein and lipid concentra-tions in rats[J].Hem,guk sikp,um Yongyang KwahakHoeehi,1998,27(3):525.
    [106]Sohn Hee Sook.Efects ofIxefis sonehifolia Hance.dieton lipid metabolism and liver f unction of rats administeredwith ethanol[J].Hanguk Yon,gyang Hankhoechi,2001,34(5):493.
    [107]Bae Song—Ja,Rob Sung—bae,Jung Bok—Mi.Efectsof godulbaegi extracts on the stability an d fluidity of phos—pholipid liposomal membranes[J].Hem,guk Sikp,um Yongyang Kwahak Hoechi,1998,27(3):508.
    [108]谢湘林,周鸣,刘宏雁.苦碟子口服液对小鼠及大鼠学习记忆的影响[J].吉林大学学报,2004,30(5):721.
    [109]王黎,陈满秋.碟脉灵注射液对犬实验性心肌梗死的保护作用[J].中国医院药学杂志,2002,22(2):80
    [110]柳晓琳,金艳书.苦碟子抗肿瘤作用的实验性研究[J].锦州医学院学报,2002,23(1):7
    [111]Yee,Su bog;Lee,Jung Hua;Chung,Hae Yong.Inhibitory effectsof luteolin isolated from Ixeris sonchifoliaHance.on the prolifera-tion of HEPG2human hepatocellular carcinoma cells[J].Archivesof pharmacal Research,2003,26(2):151
    [112]SoHn,Hee sook;Jung Bok Mi.Effects of Ixeris sonchifolia dieton lipid metabolism and liver function of administered withethanol[J].Hanguk YonggYang Hakhoechi,2001,34(5):493
    [113]Bae,Song-Ja;Roh,Sung-Bae,Jung,Bok-Mi.Effects of godulbae-gi extracts on the stability and fluidity of phospholipids mem-branes[J].Han'guk Sikp'um YongYang kwshak Hoechi,1998,27(3):508
    [114]冯玉书,桂绿荷.抱茎苦荬菜对心血管系统的药理作用[J].中草药通讯,1979,3:31.
    [115]马辉,等.苦碟子化学成分和药理研究述要[J].辽宁中医院报,2005,7(3):224-225.
    [116]魏蓉,林港祥,秦忠明.苦碟子注射液对血瘀症血液流变学及血管内皮素的影响[J].贵阳中医学院学报,2001,23(4):59-60.
    [117]程芳,张红梅,张宏文,等.苦碟子治疗冠心病心绞痛56例及其远期疗效观察[J].中国疗养医学,1999,8(4):28-29.
    [118]胡国友,白红梅,柳青.苦碟子对老年人2型糖尿病患者血脂及血黏度的影响[J].实用医药杂志,2005,5(22):413.
    [119]雷秀玲,董雪峰,陈植和,等.络泰对大鼠实验性急性心肌缺血的保护作用及抗脂 质过氧化作用[J].天然产物研究与开发,2001,13(4):58.
    [120]鹿小燕,张文高,周苏宁,等.口服人参、三七提取物与牛磺酸对兔心肌缺血再灌注损伤中ET、CGRP的影响[J].山东中医药大学学报,2001,25(5):379.
    [121]刘季春,陈朋.维拉帕米和三七总皂甙对犬心肌的保护作用[J].中华麻醉学杂志,1997,17(12):741.
    [122]雷秀玲,董雪峰,杨雁华,等.三七总皂甙和灯盏花素复方注射剂对结扎大鼠冠脉致心肌缺血的保护作用[J].天然产物研究与开发,2002,14(3):54-57.
    [123]唐旭东,姜建青,姜大春,等.三七总皂苷对心肌缺血—再灌注中中性粒细胞核因子—kB活化及其粘附的影响[J].中国药理学通报,2002,18(5):556-559.
    [124]冯培芳,秦南屏,乔樵,等.三七总皂甙改善高血压病左室舒张功能的临床与实验研究[J].中国中西医结合杂志,1997,17(2):717.
    [125]冯培芳,蒋惠芳.三七总皂甙对心肌细胞内及其肌浆网膜上钙泵活性的影响[J].中国中药杂志.1998.23(3):173-175.
    [126]陈江斌,许家王利,江洪,等.三七总皂苷对冠心病患者过氧化脂质及纤维蛋白溶酶原激活物的影响[J].中国新药杂志,2000,9(11):781-782.
    [127]刘建辉,翼风云,王亭,等.三七总皂苷对实验性脑缺血脑血流及血脑屏障的影响作用[J].河北医药,2002,24(4):249.
    [128]姚小皓,李学军.三七中人参三醇苷对脑缺血的保护作用及其机制[J].中国中药杂志,2002,27(5):371-373.
    [129]马丽焱,王春兰,张琪,等.三七皂甙对脑组织血液供应和能量代谢的影响[J].中国药理学通报,1998,14(1):27-29.
    [130]林曙光.三七皂甙对高脂血清所致的培养主动脉平滑肌细胞增殖的作用[J].中国药理学报,1993,14(4):314.
    [131]Lowenstein CJ,Snyder SH.Nitric oxted,anovel biologic messenger[J].Cell,1992,70:705.
    [132]Juhan Ⅵ,aladdierJ,Alessi MC,etal.DeficientTPAreleaseand elevated PA inhibitor Levels inpatients with spon-taneous Or concunent deep venoos thrombosis[J],1hromb Haomost,1987,57:67.
    [133]Radom ski MW,Palmer RMJ,Moncada S.Comparative pharmacology Of endothelium-derived relaxing fac-tor,nitric oxied and prostacyclin in platelets[J]. J.Pharmacol,1987,92:181.
    [134]WalterV.C.Yclic nucle otid eprotein phosphory lation[J].ghorylationRes,1994,17:249.
    [135]袁新初,周乾毅,杨逢春,等.严重烫伤大鼠组织Na~+,K~+-ATPase和Ca~(2+)-ATPase 活性改变及三七保护作用探讨[J].中草药,2002,33(7):637-638.
    [136]袁新初,周乾毅.烫伤大鼠脂质过氧化改变及三七保护作用探讨[J].中草药,2002,33(5):446-447.
    [137]秦勇,王金宇,黄方文,等.三七总皂甙注射液治疗缺血性心脏病56例临床观察[J].中国基层医药,2001,8(5):461-461.
    [138]汪坚敏,王俏,朱健,等.三七总皂甙对冠心病不稳定性心绞痛内皮功能的影响[J].临床中老年保健杂志,2002,5(3):183-184.
    [139]谢庆成,张文高.刘建平,等.黄芪与三七总皂甙配伍对不稳定性心绞痛患者左心室舒张与收缩功能的影响[J].山东生物医学工程,2002,21(2):28-30.
    [140]唐敏.唐晓玲,陈荣.三七总皂苷治疗心血管疾病临床研究进展[J].中国中医药信息,2006,13(9)93-96.
    [141]Feng Xi-zhi,Xu Sui-xu,Dong Mei.Tow Novel Flavonoids from Ixeris sonchifolia[J].Journal of Chinese Pharmaceutical Scices,2000,9(3):134-136.
    [142]Lu J,Feng X,Sun Q,et al.Efect of six flavonoid corn—pounds from hefts sonchifolia on stimuhs—induced superoxide generation and tyrosyl phosphorylation in human neu-trophils[J].Clin Chim Aaa,2002,316(1-2):95.
    [143]Ma Jiyuan,Wang Zhengtao.Sesquiterpene lactones from Ixeris sonchifolia[J].Phytochemistry,1998,48(1):201.
    [144]Feng XZ,Dong M,Gao ZJ,et al.Three new tfiterpenoidsaponins from Ixeris sonchifolia and their cytotoxic activity[J].Planta Med,2003,69(11):1036.
    [145]Nirmala C,Puvanakrishman R.Protective role of curcum in a-gainstisoproterenol induced myocardial infarction in rats[J].Mol Cell Biochem,1996,159(2):85-93.
    [146]Krajewski S,Krajewska M,Reed JC.Immunhistochemical analysis of in vivo patterns of Bak expression,a proapoptotic member of the Bci-2 protein family[J].Cancer Res,1996,56(12):2849-2855.
    [147]Fitch ME,Chang CM,Parslow TG.The BH3 domain is required for caspase-inde pendent cell death induced by Bax and oligomycin[J].Cell Death Differ.2000. 7(4):338-349.
    [148]辛华雯,曾繁典.细胞凋亡的分子调节与肿瘤基因治疗策略[J].医学综述,2001,7(5)263-264
    [149]Sharov VG,Sabbah NH,Shimoyama H,et al.Evidence of cardiocyte apoptosis in myocardium of dogs with chronic heart failure[J],Am J Pathol,1996,148(1):141-149.
    [150]SarasteA,PulkkiK,KallajokiM,etal.Apoptosis in human acutemyo cardia lin farction.Circulation[J],1997,95(2):320-323.
    [151]Fliss H,Gattinger D.Apoptosis in ischemic and reperfused rat myocardium[J].Circ Res,1996,79(5):949-956.
    [152]Rao L,Dobbas M,Sabbatini P,et al.The adenovirus E1A proteins induce apoptosis,which is inhibited by the E1B 19-kDa and Bcl-2 proteins[J].Proc Natl Acad Sci USA,1992,89(16):7742-7748.
    [153]James TN.Normal and abnormal consequences of apoptosis in the human heart:from postnatal morphogenesis to paroxysmal arrhythmias[J].Trans Am Clin Climatol Assoc,1993,105:145-177.
    [154]James.TN,Terasski F,Pavlovich ER,et al.Apoptosis and pleomorphic micromitochondriosis in the sinus nodes surgically excised from five patients with the long QT syndrome[J].J Lad Clin Med,1993,122(3):309-323.
    [155]Long X,Boluyt MO,Hipolito ML,et al.p53 and the hypoxia-indueced a Doptosis of cultured neonatal rat cardiac myocyes[J].J CLin Invest,1997,99(11):35-43.
    [156]Tanaka M.Ito H.Adaehi S.et al.Hypoxis apoptosis with enhanced expression of antigen-messenger RNA incultured neonatal rat cardiomyo-eytes[J].C ireRea,1994:75:426.
    [157]Cheng w,Li B,Kajasturs J,et al,Stretch induced programmed myocyte cell deathe[J].J clin Ivest,1995:96:2247.
    [158]Fliss H,Gattinger D.Apoptosis in ischemic arid reperfused rat myocardiuin[J].Cire Res1996:79:94914-17.
    [159]Kerr JF,Wyllie AH.Apoptosis:a basic biological phenomeon with widerangin gimplications in tissue kinetics[J].Br J Cancer,1972,26(4):239-257.
    [160]WylliecHA.Apoptosis:cellcdeathcinctissuc regulation[J].J Pathol.1987,1 53(4):31 3-3 16.
    [161]Olivett G,Quaini F,et at.Acute myocardial in farction in humans is associated with Acti-vation of Progrmamed myocyte cell death in the surviving portionof the heart[J].JMol CellCardiol.1996,28(9):2005-2016.
    [162]SabbahHN,SharyVG,LesehM,et al.Progression of heart failure arole forinter stitial fibr-osis[J].Mol Cell Bioehem,1995,147(12):29-34.
    [163]Saraste A,Pulleki K,et al.Apoptosis in human acute myocardial in farction[J].J.Circulation.1997,95(2):320-323.
    [164]SUN Jian-yi,JINGMing-yan.Natural inhibitors of caspases and cell apoptosis[J].Chinese Journal of Pathophysiology.2005,21(5):1036-1040.
    [165]QU Chao-fa,MA Li-kun,XU Shao-dong,WU Xue-ping.Cardiomyocyte apoptosis and expression of Bcl-2,Bax protein after acutemyocardial infarction and late reperfusion in dogs[J].Chinese Journal of Pathophysiology,2007,23(4):656-659.
    [166]Kohji Matsushita,Wei Meng,Xiaoying Wang,et al.Evidence for apoptosis after intracerebral hemorrhage rat striatum[J].J Cereb Blood FlowMetab,2000,20:196-204.
    [167]Dale E Bredesen.Neural apoptosis[J].Annals of neurology,1995,38(2):839-851.
    [168]TANG Xiao qin,ZHAO Jian hong,ZHANG Zheng yi,ZHANG Xu.Effect of naloxone on expression of Bcl-2 protein and tumor necrosis factorαin rats with acute myocardial ischemia/reperfusion injury[J].Chin Crit Care Med,2005,17(7):430-433.
    [169]SHI Fei,LIU Zhi-yue.Effect of Bcl-2 Protein on Myocardial Ischemia[J].Acta Acad Med Nei Mongol Dec,2005,27(5):93-95.
    [170]何志巍.Caspases与细胞凋亡研究进展[J].国外医学:生理、病理科学与临床分册,1999,19(1):15-19.
    [171]Tsujinoto Y,Finger LR,Yunis J,et al.Cloning of the chromosome breakpoint of neoplastic B cells with the t(14;18) chromosome translocation[J].Science,1984,226(4678):1097-1099.
    [172]Kajstura J,Cheng W,Reiss K.Apoptosis and necrotic myocyte cell death in dependent contributing variable of in fract size in rats[J].Lab Invest,1996,74(1):86-107.
    [173]Hockenbery DM,Oltvai IN,YIN YM,et al.Bcl-2 functions in an antioxidant pathway to present apoptosis[J].Cell,1993,75(2):241-251.
    [174]张学敏.细胞凋亡研究中的一些热点问题[J].中国药理学与毒理学杂志,2000,14(2):81-85.
    [175]Yuan J,Shaham S,Ledoux S.The C.elegans cell death gene ced-3 encodes a protein similartomammalian interleukin-1 betaconverting enzyme[J].Cell,1993,75(4):641-652.
    [176]Nicholson DW,Thornberry NA.Caspases:killer proteases[J].Trends Biochem Sci,1997,22(8):299-306.
    [177]张拥波,罗勇,董为伟.caspase-3在脑缺血神经元损伤中的作用.国外医学[J].脑血管疾病分册,2000,8(2):79-81.
    [178]CHENG Gang,XUGeng,SHAN Jiang,HUANG Jin-yu,ZHOUHua,Apoptosis induced by simvastatin in rat vascular smooth muscle cells through calpain and caspase-3-dependent pathways[J].Chinese Journal of Pathophysiology,2003,19(9):1189-1192.
    [179]Cheng EHY,Kirsch DG,Clem RJ,et al.Conversion of Bcl-2 to a Bax-like death effector by caspases[J].Science,1997,278(5345):1966-1968.
    [180]Kirsch DG,Doseff A,Chau BN,et al.Caspase-3-dependent cleavage of Bcl-2 promotes release of cytochrome C mitochondrial cytochrome release[J].J Biol Chem,1999,274(30):21155-21161.
    [181]Slee EA,Keogh SA,Martin SJ.Cleavage of BID during cytotoxic drug and UV radiation-induced apoptosis occurs downstream of the point of Bcl-2 action and is catalysed by caspase-3:apotential feedback loop for amplification of apoptosis-assciated[J].Cell Death Differ,2000,7(6):556-565.
    [182]LIUXing-de,CHENYun-zhen.The Effects of Breviscapine on Cardiac Myocyte Apoptosis and Expression of Bcl-2during Myocardial Ischemia/Reperfusion Course in Rats[J].Journal of Gui yang Medical College,2004,29(2):102-104.
    [183]ZHANGQi-hao,LUDa-xiang,WANGHua-dong,QI Ren-bin,FUYong-mei,Effect of glycine on nitric oxide system andBcl-2mRNA expressionin myocardial ischemic-rep erfusion injury[J].Chinese Journal of Pathophysiology,2004,20(1):42-46.
    [184]Anversa P,Cheng M.Apoptosis and myocardial infarction[J].Basic Res Cardiol,1998,9(13):8-12.
    [185]周艳铃,徐明.大鼠急性心肌缺血再灌注心肌细胞凋亡与Bcl-2/Bax蛋白的表达[J].武警医学,2001,12(3):131-134.
    [186]Jun M,Yukihiro H,Michiya O,et al.Expression of Bcl-2 protein,an inhibitor of apoptosis,and Bax,an accelerator of apoptosis in ventricular myocytes of human hearts with myocardial infarction[J].Circulation,1996,94(7):1506.
    [187]Li Jinwei,Zhu Peichun,Si Yinchu,et al.Research on the Effects of the Total Saponin from Sanqi(the dried Root of Panax Notoginseng) on Proapoptotic Caspase-3 in the Forebrain in the Rats with Intracerebral Hemorrhage[J].Journal of Beijing University of TCM,2003,26(2):22-25.
    [188]Apoptosis,Excitotoxicity,Newropathotogy.Marcel Leist Perluigi Nicotera[J].Experimental Cell Research,1998,239:183-201.
    [189]Francois G Gervais,Daigen Xu.George S.Robertson,et al.Involvement of caspases in proteolytic cleavage of Alzheimer's amyloid-βprecursor protein and amyloidogenic Appeptide formation[J].Cell,1999,97:395-406.
    [190]林荣等主编.心血管疾病的现代观点[M].北京大学医学出版社,2005,66-69.
    [191]杨振华.再谈对不稳定心绞痛的诊断问题[J].中华医学杂志,1995,2:69.
    [192]李淑敏,唐朝枢,等.金属硫蛋白对异丙肾上腺素心肌损伤的保护作用[J].中国药理学通报.1996;12(4):332.
    [193]于严,等.牛磺酸抗肝脏缺血再灌注损伤及其机理.的实验研究[J].中国病理生理杂志.1991,7(6):566.
    [194]孙伟夫,李晓峰,李彩燕等.心复康抗心肌缺血的实验研究[J].中国中医药科技.2001,8(5):298.
    [195]王坤等.实用诊断酶学[M].重庆科学技术文献出版社.1989,134-135.
    [196]贲长恩 北京中医药大学.组织学与胚胎学[M].北京学苑出版社.1975.57.
    [197]Rona C.An infact like myocardial lesion and other toxic manifestations produced by isoproterend in the rat[M].Areh Pathol Lab Med.1959,67:443.
    [198]Wilson S,Colucel MD.Apoptosis in the heart[J].N Eng J Med,1996,17(10):1224-1226.
    [199]Haider N,Narula J,Hajar RJ,et al.Apoptosis in human explanted cardiomyopathic hearts Suggests programmed progression of dilated cardiomyopathy[J],Circula tion,1995,92(supp Ⅱ):1724-1729
    [200]Ji HB,Zhai QW,Liu XY,et al Transcription regulation of Bcl-2 gene[J].Acta Bioehim Biophys Sin,2000,32(2)95-99.
    [201]CrossA,Medonnell JM,Korsmeyer5 J.Bcl-2 fmaily members and themitoe hondriain apoptosis[J].Genes Dev,1999,13(15):1899-1911.
    [202]Stahler F,Roe mer K.Mutant P53 can provoke apoptosis in P53-deficient Hep B cells with delayed kinetics relative to wild-typeP53[J].oncogene,1998,17(26):3507-3412.
    [203]Msao J,Hayakawa Y,ohno M,et al.Expression of Bcl-2 protein,an inhibitor of apoptosis,and Bax,an accelerator of apoptosis,in ventricular myocytes of human hearts With myocardial infarction[J].Circulation,1996,94(7);1506-12.
    [204]Kirshenbaum LA.Regulators of apoptosis in the heart:a matter of life and death[J].Can J Cardiol,1998,14(3):457-460.
    [205]Wyllie HA.The genetic regulation of apoptosis[J].Curr opin Genet Dev,1995,5:97-104.
    [206]马瑞君,王效.当归的研究进展[J].中草药.2003,3(3):280-283.
    [207]郭棋等.药物对病毒感染培养心肌细胞Ca~(2+)内流及CVB_3 RNA复制的影响[J].中国病毒学.1996,11(1):40.
    [208]Steller H.Mechanis ms and genes of cellular suicide[J].Science,1995,267:1445-9.
    [209]Tskemura G,ohno M,Fujiwara Ⅱ.Ischemic heart disease and apoptosis[J].Ri nshoo n,1997,45(7):606-13.
    [210]Cheng EHY,Kirsch DG,Glem RJ,et al.Conversion of BCl-2 to abaxlike death effector by caspases[J].Science,1997,278:1966-8.
    [211]Chengw,KajsturaJ,eta].Programmed myocyte cell death afreets the viable myocardium afteri nfaretion in rats[J].ExpCellRes.1996,226(2):316-32.
    [212]KajstuxaJ,ChengW,ReissK,etal[J].LabInvest,1996,74:86-107.
    [213]CommunalC,SinghK,PimenterDR,etal[J].Cireulation.1998,98(13):1329-1334.
    [214]TodorA,SharovVG,anheheoEJ,SilvemranN,BernabeiA,SabbahHN.Hypoxiaind uee-deleavage of eaPase3 and DFF45 CAD inhumanfailile deardio myoeytes[J].JPhsiola HeartCire Phsiol,2002,283(3):H990-995.
    [215]Dimmelers.HemrannC,ZeiherMA.Apoptosis of end othelial cells:contribution to the path-ophysiology of atheroselerosis[J].EurCytokineNetw,1998,9:697-698.
    [216]LID,YangB,MehtaJL.Tumorneerosis factor-alpha enhances hyproxia-reoxvg enatio-n Med-iated a poptosisi neultured human eoronaryarteryendothelial cells:Critiealrole of proteinkin-ase[J].Cardiovase Res,1999:42(3):805-813.
    [217]Weissbere Pi.et al.Cardiovasc Res[J].1993:27:1191.
    [218]Kim H R,Luo Y,Kessel D.Enhanced apoptotic responseto photodynamic therapy after Bcl-2transfection[J].Cancer Res,1999,59:3429-3432.
    [219]Xue L Y,Chiu S M,Oleinick N L.Photochemical destruc-tion of the Bcl-2oncoprotein during photodynamic therapywith phthalocyanine photosensitizer Pc4[J].Oncogene,2001,20:3420-3427.
    [220]Kessel D,Castelli M.Evidence that Bcl-2is the target ofthree photosensitizers that induce a rapid apoptotic re-sponse[J].Photochem Photobiol,2001,74(2):318-322.
    [221]Usuda J,Chiu S M,Murphy E S,et al.Domain-dependent photodamage to Bcl-2[J].J Biol Chem,2003,278(3):201-202.
    [222]Kessel D,Reiners Jr J.Apoptotic response to photody-namic therapy versus the Bcl-2antagonist Hal 4-1[J].Photochem Photobiol,2002,76(3):314-319.
    [223]CAI Xiong-weil,LIU Cheng-yi,et al.Effect of Photodynamic HMME-PDT on Bcl-2.Journal of Optoelectronics[J].Laser,2005,16(3)376-379.
    [224]LIN Chun-long,ZHANG Zhen-xiang.Focal adhesion kinase antisense ligodeoxy nucleotidepromotes apoptosis in human pulmonary artery smooth muscle cells[J].Chinese Journal of Pathophysiology 2006,22(2):288-291
    [225]DUANXiao-Yu,LINShi-He,ZHAO Jie-Xu,et al Neurotoxicity of PrP106-126 on the Primary Neuron Culture[J].Chin J Clin Neurosci 2005,13(2),140-143
    [226]GUO Xiao-peng,HUANG Guo-xiang,WU Qing,et al.Effect of manganese on growth of HUVEC-304cells and expression of caspase[J].Chin J Public HealthJan 2007,23(1):110-111.
    [227]XIAO Yan-feng,LIU Ya,TIAN Wei,REN Li-fen.Expression of Survivin,Anti poptosis Gene in Leukemia and Correlation between Expression of Survivin,Fas and Caspase[J].Appl Clin Pediatr,2005,20(1):13-15.
    [228]ZHANG Shen,et al.Suppressive Effects of Ginkgo biloba Extract on H_2O_2-Induced Apop-tosis in RAW264.7 Macrophages[J].China Pharm J,2006,41(10):750-754.

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