芪桂益脉灵对急性心肌缺血再灌注大鼠心肌细胞凋亡基因表达的影响
摘要
目的观察芪桂益脉灵对急性心肌缺血再灌注大鼠心肌细胞凋亡相关基因Fas、Bcl-2蛋白表达的影响,探讨其心肌保护作用及其机制。
方法选取Wistar大鼠70只,雌雄各半,随机分为七组(每组10只)并编号:空白对照组、假手术组、缺血再灌注组、缺血预适应组、消心痛组、芪桂益脉灵低剂量组和芪桂益脉灵高剂量组,采用左冠状动脉穿线结扎法制备大鼠心肌缺血再灌注模型,造模成功后取心尖部组织,用HE染色法光镜下观察凋亡细胞的形态学变化;用免疫组化染色法检测心肌细胞凋亡相关基因Fas、Bcl-2蛋白阳性表达情况。
结果1.除假手术组和空白对照组外,其余各组心肌细胞都有不同程度的形态学变化,以缺血再灌注组细胞形态损伤为著。
2.芪桂益脉灵高、低剂量组,消心痛组,缺血预适应组与缺血再灌注组比较Bcl-2蛋白表达增高,差异显著(P＜0.05);芪桂益脉灵高剂量组可明显上调Bcl-2蛋白表达,与低剂量组比较差异显著(P＜0.05),与消心痛组比较,两者间无显著差异(P＞0.05)。
3.缺血再灌注组Fas蛋白表达最高,与其余各组比较有显著性差异(P＜0.05),芪桂益脉灵组能明显下调Fas蛋白表达,且以高剂量组显著,其作用与消心痛组、缺血预适应组相当,三者间比较差异不显著(P＞0.05)。
结论1.芪桂益脉灵可减轻急性心肌缺血再灌注模型大鼠的心肌结构的异常。
2.芪桂益脉灵可通过下调Fas基因蛋白表达与上调Bcl-2基因蛋白表达抑制心肌细胞凋亡,具有一定的抗心肌损伤作用。
3.芪桂益脉灵调控凋亡基因的作用与缺血预适应组、消心痛组相当,提示其具有药理预适应样心肌保护作用。
Objective:
To observe the effect of QiGuiYiMaiLing(QGYML) on acute myocardial ischemic -reperfusion in rat cardiac myocyte apoptosis related genes Fas,Bcl-2 protein expression to explore their effects and mechanism of myocardial protection.
Methods:
The left coronary artery ligation were prepared threading myocardial ischemic -reper -fusion model,Wistar rats with 70,half male and female,were randomly divided into seven groups(n=10) and ID:blank control group,sham-operated group,ischemia- reperfusion group,ischemic preconditioning group,isosorbide dinitrate group,low-dose QGYML and QGYML high-dose group,We observe the morphological changes of apoptotic cells by HE staining in electron microscopy and check cardiomyocyte apoptosis related genes Fas, Bcl-2 protein positive expression by immunohistochemical staining.
Results:
1.In addition to the sham-operated group and blank control group,the remaining myocytes in each group has a different degree of morphological changes.Especially, ischemic -reperfusion injury group was significant for the cell morphology.
2.QGYML high-and low-dose group,isosorbide dinitrate group,ischemic preconditioning group increased significantly than ischemic-reperfusion group Bcl-2 protein expression(P＜0.05);Effects of QGYML high-dose group may significantly increase the expression of Bcl-2 protein,and compared with low-dose group,the result is significantly different(P＜0.05),and compared with isosorbide dinitrate group,there was no significant difference(P＞0.05).
3.Ischemic-reperfusion group Fas protein expression is the highest,compared with the other groups,and significantly different(P＜0.05),QGYML significantly reduced its expression,and high-dose group was significant,compared with isosorbide dinitrate group and ischemic preconditioning group,the result is equivalent comparison and among the three were no significant differences(P＞0.05).
Conclusion:
1.QGYML can reduce the acute myocardial ischemic-reperfusion rat model of myocardial structural abnormalities.
2.QGYML,through reduced expression of Fas gene protein and increased Bcl-2 gene protein expression,inhibited cardiomyocyte apoptosis and has a certain role in anti-myoca rdial ischemia.
3.The role of QGYML gene regulation of apoptosis is similar to ischemic preconditioning group and isosorbide dinitrate group,may have its pharmacological preconditioning -like myocardial protection.
方法选取Wistar大鼠70只,雌雄各半,随机分为七组(每组10只)并编号:空白对照组、假手术组、缺血再灌注组、缺血预适应组、消心痛组、芪桂益脉灵低剂量组和芪桂益脉灵高剂量组,采用左冠状动脉穿线结扎法制备大鼠心肌缺血再灌注模型,造模成功后取心尖部组织,用HE染色法光镜下观察凋亡细胞的形态学变化;用免疫组化染色法检测心肌细胞凋亡相关基因Fas、Bcl-2蛋白阳性表达情况。
结果1.除假手术组和空白对照组外,其余各组心肌细胞都有不同程度的形态学变化,以缺血再灌注组细胞形态损伤为著。
2.芪桂益脉灵高、低剂量组,消心痛组,缺血预适应组与缺血再灌注组比较Bcl-2蛋白表达增高,差异显著(P＜0.05);芪桂益脉灵高剂量组可明显上调Bcl-2蛋白表达,与低剂量组比较差异显著(P＜0.05),与消心痛组比较,两者间无显著差异(P＞0.05)。
3.缺血再灌注组Fas蛋白表达最高,与其余各组比较有显著性差异(P＜0.05),芪桂益脉灵组能明显下调Fas蛋白表达,且以高剂量组显著,其作用与消心痛组、缺血预适应组相当,三者间比较差异不显著(P＞0.05)。
结论1.芪桂益脉灵可减轻急性心肌缺血再灌注模型大鼠的心肌结构的异常。
2.芪桂益脉灵可通过下调Fas基因蛋白表达与上调Bcl-2基因蛋白表达抑制心肌细胞凋亡,具有一定的抗心肌损伤作用。
3.芪桂益脉灵调控凋亡基因的作用与缺血预适应组、消心痛组相当,提示其具有药理预适应样心肌保护作用。
Objective:
To observe the effect of QiGuiYiMaiLing(QGYML) on acute myocardial ischemic -reperfusion in rat cardiac myocyte apoptosis related genes Fas,Bcl-2 protein expression to explore their effects and mechanism of myocardial protection.
Methods:
The left coronary artery ligation were prepared threading myocardial ischemic -reper -fusion model,Wistar rats with 70,half male and female,were randomly divided into seven groups(n=10) and ID:blank control group,sham-operated group,ischemia- reperfusion group,ischemic preconditioning group,isosorbide dinitrate group,low-dose QGYML and QGYML high-dose group,We observe the morphological changes of apoptotic cells by HE staining in electron microscopy and check cardiomyocyte apoptosis related genes Fas, Bcl-2 protein positive expression by immunohistochemical staining.
Results:
1.In addition to the sham-operated group and blank control group,the remaining myocytes in each group has a different degree of morphological changes.Especially, ischemic -reperfusion injury group was significant for the cell morphology.
2.QGYML high-and low-dose group,isosorbide dinitrate group,ischemic preconditioning group increased significantly than ischemic-reperfusion group Bcl-2 protein expression(P＜0.05);Effects of QGYML high-dose group may significantly increase the expression of Bcl-2 protein,and compared with low-dose group,the result is significantly different(P＜0.05),and compared with isosorbide dinitrate group,there was no significant difference(P＞0.05).
3.Ischemic-reperfusion group Fas protein expression is the highest,compared with the other groups,and significantly different(P＜0.05),QGYML significantly reduced its expression,and high-dose group was significant,compared with isosorbide dinitrate group and ischemic preconditioning group,the result is equivalent comparison and among the three were no significant differences(P＞0.05).
Conclusion:
1.QGYML can reduce the acute myocardial ischemic-reperfusion rat model of myocardial structural abnormalities.
2.QGYML,through reduced expression of Fas gene protein and increased Bcl-2 gene protein expression,inhibited cardiomyocyte apoptosis and has a certain role in anti-myoca rdial ischemia.
3.The role of QGYML gene regulation of apoptosis is similar to ischemic preconditioning group and isosorbide dinitrate group,may have its pharmacological preconditioning -like myocardial protection.
引文
[1]杨彦玲,师养荣,李建龙,等.心肌缺血再灌注损伤研究进展[J].心血管病学进展,2003,24(2):116-121.
[2]徐京育,等.芪桂益脉灵抗快速心律失常的临床与实验研究.黑龙江中医药大学博士学位文.2003,6:50.
[3]孙琳琳,芪桂益脉灵对心肌缺血再灌注大鼠心肌梗死面积及血清一氧化氮含量的影响.黑龙江中医药大学硕士学位论文.2008,6:28.
[4]孙涛,苏全生,自由基与心肌缺血/再灌注损伤[J].实用医院临床杂志,2006,3(4):94-96.
[5]Mochizuki S.Jiang C.Na~+-Ca~(2+) exchanger and myocardial ischemic Reperfusion [J]Jpn heart J.1998,39(6):707-714.
[6]谷天祥,张显清,谷春久,等.心肌缺血再灌注损伤亚细胞Ca~(2+)反常与ATP酶泵功能抑制[J].中华心血管病杂志,2001,29(7):420-423.
[7]Beresewicz A,Czarnowska E,Maczewski M.Ischemic preconditioning and supemxide dismutase protect against endothelial dysfunction and endothelium glycocalyx disruption in the post ischemic guinea-pig hearts[J].MolCell Biochem,1998,186:87-97
[8]ScarabelliTM,KnightR,Stephanou A,etal Clinical implications of apoptosis in ischemic myocardium[J]·Curr Probl Cardio,2006,31(3):181-264.
[9]Buja LM,Entman ML.Modes of myocardial cell injury and cell death in ischemic heardisease[J].Circulation 1998,98:1355-7.
[10]Hunot S,Flavell RA.Apoptosis.Death of a monopoly[J]Science 2001,292:865-6.
[11]Kajstura J,Cheng W,Reiss K,etal.Apoptotic and necroticmyocyte tell deaths are independent contributing viarables ofInfaret size inrats.Lab Invest,1996,74:86-107
[12]Gotilieb RA,Burleson KO,kloner RA,etal Reperfusion injuryInduces apoptoois in rabbit cardiomyocytes[J]Clinlnvest,1994,941:1621-1628
[13]Zhao ZQ,Nakamura M,Wang NP,etal.Progressively developed myocardied apoptotic cell death during late phase of reperfusion Apoptosis,2001,6:279-290
[14]Ling H,Lou Y.Total flavonesfrom Elsholtzia blanda reduce infart size during acute myocardial ischemia by inhibiting myocardial apoptosis in rat[J]EthnoPbannacol,2005,101:169-175
[15]HuY,Benediet MA,Wud,etal.Bel-X,interacts with Apaf-land inhibits Apaf-l-dePendent caspase-9 activation.ProeNatlAeadSei USA,1998,95:4386-4391
[16]GreenDReedJC.Mitoehondria and apoptosis.Seience,1998,281:1309-1312
[17]Kuida Khaydar TFKuanC-Yetal.Reduced apoptosis and cytoehrome-emediatedeas Pase activation inmieelackingeas Pase 9 Cell,1998,94:325-337
[18]CaiJ Jones DP.SuPeroxide in apoptosis.JBiolChem,1998,273:11401-11401
[19]Chen M,Wang J.Initiator caspases in apoptosis signaling Pathways.Apoptosis,2002,7:313-319.
[20]Salvesen GS,Dixit VM.Caspase activation:the induced proximitymodel.Proc Natla cadsci USA,1999,96:10964-10967.
[21]Hengartner,M.O.The biochemistry of apoptosis.Nature 2000,407:770-776.
[22]KaufmannS.H,Earnshaw,WC.Induction of apoptosis by cancer chemotherapy.Exp.Cell Res,2000,256:42-49.
[23]Yamashiro S,NoguchiK,MatsuzakiT,etal Beneficial effectof tetra-hydrobiopterin on ischemia-reperfusion injury in isolated perfused rathearts.JThorac Cardiovasc Surg,2002,124(4):775-784
[24]Guan W,OsanaiT,KamadaT,etal Effect of all opurinolpre treatmenton free radical generation after primary coronary angioplasty for acutemyocardial infarction.J Cardiovasc Pharmaco,2003,41[5]:699-705
[25]中华人民共和国国家标准中医临床诊疗术语疾病部分[5].北京:中国标准出版社,1997:865
[26]朱文锋.国家标准应用·中医内科疾病诊疗常规[5].湖南科技出版社,1998:247.
[27]牛惠志,李晓明,陈响中,等.生脉胶囊治疗冠心病心绞痛临床疗效观察[J].中国中西医结合杂志,2000,20(4):290.
[28]邱志楠,潘俊辉,杨权生.扶阳益气汤治疗冠心病心绞痛96例疗效观察[J].新中医,1997,29(11):17.
[29]李锡东,姚洪斌.通心络胶囊治疗冠心病心绞痛血瘀证的临床观察[J].中国中医基础医学杂志,1999,5(8):41.
[30]方药中,邓铁涛,李克光,等.实用中医内科学[M].上海:上海科学技术出版社,1985:341-341.
[31]王进.疏肝通瘀汤治疗冠心病稳定性心绞痛临床观察[J].中成药,2005,27(1):120-121.
[32]赵明中,高承梅,张宇洋,等.通心络胶囊对缺血再灌注心肌细胞凋亡及相关基因蛋白表达的影响[J].中华心血管病杂志,2000,28[3]:206.
[33]孙蓉,李云霞,段长农,等.参葛胶囊对缺血及再灌性心律失常大鼠的影响[J].中国新医药,2003,2(8):13
[34]马文英,杨家声,弓翠春等.复方丹参滴丸对血脂及血流动力学的影响[J].解放军药学学报,2001,17[1]:47-48
[35]马世玉,向继洲,吴基良,等.丹参对大鼠心肌缺血再灌注损伤后血浆一氧化氮和心肌C-fos mRNA表达的作用[J].华中科技大学学报(医学版),2003,32(5):474-477.
[36]赵蕾,杜文峰,许德义.冠心丹参片对大鼠心肌缺血再灌注损伤的保护作用[J].中国药学杂志,2006,41(36):1468-1471.
[37]王万铁,林丽娜,等.川芎嗪对实验性心肌缺血再灌注损伤中一氧化氮和内皮素的干预[J].中国病理生理杂志,2001,17(3):230-234.
[38]王万铁,林丽娜,等.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.
[39]Huang YS,Yang ZC,Yan BG,etal Improvement of early postbur cardiac function by use of Panax notoginseng and immediate totalescharexcision in one operation[J].Burns,t999,25:35-41.
[40]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.
[41]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
[42]Murry CE,Jennings RB,Reimer KA.Preconditioning with ischemia:a delay of lethal cell injury in ischemic myocardium.Circulation,1986,74:1124-1136
[43]Wan X,Bryant SM,HartG.The effects of[K~+]o on regionad ifferences in electrical characteristics of ventricular myocytesinguinea-pig[J]Exp Physiol,2000,85(6):769-774.
[44]顾国嵘,黄培志,葛均波,等.缺血及三七总皂甙预处理对心肌缺血再灌注损伤的保护作用[J].中华急诊医学杂志,2005,14(4):307-309.
[45]陈峰,王成天,王焱林,等.三七总皂甙及单体Rb1对大鼠心肌缺血再灌流的保护效应[J].医学新知,2001,11(1):33-35.
[46]刘桦,吴晓东等,黄芪苷对大鼠心肌缺血再灌注损伤的保护作用[J].中国药理学通 报,2002,18(2):198-200.
[47]高秀梅,张伯礼,商洪才,等.复方丹参滴丸对缺血预适应大鼠心肌蛋白激酶C表达的影响.中草药2003,34(10):933-935
[48]HaunstetterA,IzumoS.Toward antiaPoPtos as new treatment modatity.Circ Res 2000:86(4):371-376
[49]刘兴德,陈运贞.大鼠心肌缺血预适应对I/R心肌细胞凋亡及bcl-2表达的影响[J].中国病理生理杂志,2001,17(9):901-903.
[50]王海华,戚仁斌,殷慧群,等.黄芪预处理对离体心脏再灌注损伤的保护作用[J]中药药理与临床,2001,17(4):21-23
[51]冯津萍,姚智,赵炳让,等.心肌缺血再灌注细胞凋亡过程一些细胞活素水平变化及黄芪的影响[J]天津医药,2001,29(7):421-423
[52]程桂荣,易胜中.黄芪预处理大鼠心肌保护效应的实验研究[J]高血压杂志,2001,9(4):316-318
[53]CHENG JB,WEI HC,ZHANG S,etal.Pharmacodynamic effect of extracts in Radix Ophiopogonis on myocardial ischemia dog[J].Chinese Journal of Pathophysiology(中国病理生理杂志),2001,17(8):810
[54]HE P,DAI ZM.Protective Effect of Ophiopogan Total Saponies on Hypoxia-Reoxygenation Induced Injury in Cultured Myocardial Cells[J].Chinese Journal of Microcirculation[微循环学],2005,15(2):45
[55]张爱东,李自成,庄宁宁,等.氧化苦参碱对豚鼠心室肌细胞膜钠通道的影响[J].中国病理生理杂志2005,21(10):1946-1949
[56]陈厦,李英骥,张文杰,等.氧化苦参碱对豚鼠心室肌细胞钠电流的影响[J].白求恩医科大学学报 2001,27(1):41-42
[57]李锐松,姚素娟,陈水英,等.氧化苦参碱对离体兔心房的作用[J].中国药理报,1986,7(3):216-215
[58]朴奎善,韩春姬,申英爱,等.轮叶党参对大鼠SOD活力和MDA含量的影响.中国中医药科技,1998,5(4):239-241
[2]徐京育,等.芪桂益脉灵抗快速心律失常的临床与实验研究.黑龙江中医药大学博士学位文.2003,6:50.
[3]孙琳琳,芪桂益脉灵对心肌缺血再灌注大鼠心肌梗死面积及血清一氧化氮含量的影响.黑龙江中医药大学硕士学位论文.2008,6:28.
[4]孙涛,苏全生,自由基与心肌缺血/再灌注损伤[J].实用医院临床杂志,2006,3(4):94-96.
[5]Mochizuki S.Jiang C.Na~+-Ca~(2+) exchanger and myocardial ischemic Reperfusion [J]Jpn heart J.1998,39(6):707-714.
[6]谷天祥,张显清,谷春久,等.心肌缺血再灌注损伤亚细胞Ca~(2+)反常与ATP酶泵功能抑制[J].中华心血管病杂志,2001,29(7):420-423.
[7]Beresewicz A,Czarnowska E,Maczewski M.Ischemic preconditioning and supemxide dismutase protect against endothelial dysfunction and endothelium glycocalyx disruption in the post ischemic guinea-pig hearts[J].MolCell Biochem,1998,186:87-97
[8]ScarabelliTM,KnightR,Stephanou A,etal Clinical implications of apoptosis in ischemic myocardium[J]·Curr Probl Cardio,2006,31(3):181-264.
[9]Buja LM,Entman ML.Modes of myocardial cell injury and cell death in ischemic heardisease[J].Circulation 1998,98:1355-7.
[10]Hunot S,Flavell RA.Apoptosis.Death of a monopoly[J]Science 2001,292:865-6.
[11]Kajstura J,Cheng W,Reiss K,etal.Apoptotic and necroticmyocyte tell deaths are independent contributing viarables ofInfaret size inrats.Lab Invest,1996,74:86-107
[12]Gotilieb RA,Burleson KO,kloner RA,etal Reperfusion injuryInduces apoptoois in rabbit cardiomyocytes[J]Clinlnvest,1994,941:1621-1628
[13]Zhao ZQ,Nakamura M,Wang NP,etal.Progressively developed myocardied apoptotic cell death during late phase of reperfusion Apoptosis,2001,6:279-290
[14]Ling H,Lou Y.Total flavonesfrom Elsholtzia blanda reduce infart size during acute myocardial ischemia by inhibiting myocardial apoptosis in rat[J]EthnoPbannacol,2005,101:169-175
[15]HuY,Benediet MA,Wud,etal.Bel-X,interacts with Apaf-land inhibits Apaf-l-dePendent caspase-9 activation.ProeNatlAeadSei USA,1998,95:4386-4391
[16]GreenDReedJC.Mitoehondria and apoptosis.Seience,1998,281:1309-1312
[17]Kuida Khaydar TFKuanC-Yetal.Reduced apoptosis and cytoehrome-emediatedeas Pase activation inmieelackingeas Pase 9 Cell,1998,94:325-337
[18]CaiJ Jones DP.SuPeroxide in apoptosis.JBiolChem,1998,273:11401-11401
[19]Chen M,Wang J.Initiator caspases in apoptosis signaling Pathways.Apoptosis,2002,7:313-319.
[20]Salvesen GS,Dixit VM.Caspase activation:the induced proximitymodel.Proc Natla cadsci USA,1999,96:10964-10967.
[21]Hengartner,M.O.The biochemistry of apoptosis.Nature 2000,407:770-776.
[22]KaufmannS.H,Earnshaw,WC.Induction of apoptosis by cancer chemotherapy.Exp.Cell Res,2000,256:42-49.
[23]Yamashiro S,NoguchiK,MatsuzakiT,etal Beneficial effectof tetra-hydrobiopterin on ischemia-reperfusion injury in isolated perfused rathearts.JThorac Cardiovasc Surg,2002,124(4):775-784
[24]Guan W,OsanaiT,KamadaT,etal Effect of all opurinolpre treatmenton free radical generation after primary coronary angioplasty for acutemyocardial infarction.J Cardiovasc Pharmaco,2003,41[5]:699-705
[25]中华人民共和国国家标准中医临床诊疗术语疾病部分[5].北京:中国标准出版社,1997:865
[26]朱文锋.国家标准应用·中医内科疾病诊疗常规[5].湖南科技出版社,1998:247.
[27]牛惠志,李晓明,陈响中,等.生脉胶囊治疗冠心病心绞痛临床疗效观察[J].中国中西医结合杂志,2000,20(4):290.
[28]邱志楠,潘俊辉,杨权生.扶阳益气汤治疗冠心病心绞痛96例疗效观察[J].新中医,1997,29(11):17.
[29]李锡东,姚洪斌.通心络胶囊治疗冠心病心绞痛血瘀证的临床观察[J].中国中医基础医学杂志,1999,5(8):41.
[30]方药中,邓铁涛,李克光,等.实用中医内科学[M].上海:上海科学技术出版社,1985:341-341.
[31]王进.疏肝通瘀汤治疗冠心病稳定性心绞痛临床观察[J].中成药,2005,27(1):120-121.
[32]赵明中,高承梅,张宇洋,等.通心络胶囊对缺血再灌注心肌细胞凋亡及相关基因蛋白表达的影响[J].中华心血管病杂志,2000,28[3]:206.
[33]孙蓉,李云霞,段长农,等.参葛胶囊对缺血及再灌性心律失常大鼠的影响[J].中国新医药,2003,2(8):13
[34]马文英,杨家声,弓翠春等.复方丹参滴丸对血脂及血流动力学的影响[J].解放军药学学报,2001,17[1]:47-48
[35]马世玉,向继洲,吴基良,等.丹参对大鼠心肌缺血再灌注损伤后血浆一氧化氮和心肌C-fos mRNA表达的作用[J].华中科技大学学报(医学版),2003,32(5):474-477.
[36]赵蕾,杜文峰,许德义.冠心丹参片对大鼠心肌缺血再灌注损伤的保护作用[J].中国药学杂志,2006,41(36):1468-1471.
[37]王万铁,林丽娜,等.川芎嗪对实验性心肌缺血再灌注损伤中一氧化氮和内皮素的干预[J].中国病理生理杂志,2001,17(3):230-234.
[38]王万铁,林丽娜,等.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.
[39]Huang YS,Yang ZC,Yan BG,etal Improvement of early postbur cardiac function by use of Panax notoginseng and immediate totalescharexcision in one operation[J].Burns,t999,25:35-41.
[40]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.
[41]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
[42]Murry CE,Jennings RB,Reimer KA.Preconditioning with ischemia:a delay of lethal cell injury in ischemic myocardium.Circulation,1986,74:1124-1136
[43]Wan X,Bryant SM,HartG.The effects of[K~+]o on regionad ifferences in electrical characteristics of ventricular myocytesinguinea-pig[J]Exp Physiol,2000,85(6):769-774.
[44]顾国嵘,黄培志,葛均波,等.缺血及三七总皂甙预处理对心肌缺血再灌注损伤的保护作用[J].中华急诊医学杂志,2005,14(4):307-309.
[45]陈峰,王成天,王焱林,等.三七总皂甙及单体Rb1对大鼠心肌缺血再灌流的保护效应[J].医学新知,2001,11(1):33-35.
[46]刘桦,吴晓东等,黄芪苷对大鼠心肌缺血再灌注损伤的保护作用[J].中国药理学通 报,2002,18(2):198-200.
[47]高秀梅,张伯礼,商洪才,等.复方丹参滴丸对缺血预适应大鼠心肌蛋白激酶C表达的影响.中草药2003,34(10):933-935
[48]HaunstetterA,IzumoS.Toward antiaPoPtos as new treatment modatity.Circ Res 2000:86(4):371-376
[49]刘兴德,陈运贞.大鼠心肌缺血预适应对I/R心肌细胞凋亡及bcl-2表达的影响[J].中国病理生理杂志,2001,17(9):901-903.
[50]王海华,戚仁斌,殷慧群,等.黄芪预处理对离体心脏再灌注损伤的保护作用[J]中药药理与临床,2001,17(4):21-23
[51]冯津萍,姚智,赵炳让,等.心肌缺血再灌注细胞凋亡过程一些细胞活素水平变化及黄芪的影响[J]天津医药,2001,29(7):421-423
[52]程桂荣,易胜中.黄芪预处理大鼠心肌保护效应的实验研究[J]高血压杂志,2001,9(4):316-318
[53]CHENG JB,WEI HC,ZHANG S,etal.Pharmacodynamic effect of extracts in Radix Ophiopogonis on myocardial ischemia dog[J].Chinese Journal of Pathophysiology(中国病理生理杂志),2001,17(8):810
[54]HE P,DAI ZM.Protective Effect of Ophiopogan Total Saponies on Hypoxia-Reoxygenation Induced Injury in Cultured Myocardial Cells[J].Chinese Journal of Microcirculation[微循环学],2005,15(2):45
[55]张爱东,李自成,庄宁宁,等.氧化苦参碱对豚鼠心室肌细胞膜钠通道的影响[J].中国病理生理杂志2005,21(10):1946-1949
[56]陈厦,李英骥,张文杰,等.氧化苦参碱对豚鼠心室肌细胞钠电流的影响[J].白求恩医科大学学报 2001,27(1):41-42
[57]李锐松,姚素娟,陈水英,等.氧化苦参碱对离体兔心房的作用[J].中国药理报,1986,7(3):216-215
[58]朴奎善,韩春姬,申英爱,等.轮叶党参对大鼠SOD活力和MDA含量的影响.中国中医药科技,1998,5(4):239-241