三种鼠尾草注射液对大鼠心肌缺血血流动力学的影响和对心肌缺血再灌注损伤的保护作用
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摘要
目的：研究云南产鼠尾草鼠药物滇丹参、甘西鼠尾、褐毛甘西鼠尾对急性心肌缺血引起的血流动力学异常的影响和对心肌缺血再灌注损伤的保护作用，并与丹参进行对比。方法：1、结扎大鼠冠脉左前降支造成急性心肌缺血模型，经股静脉给药。左心室插管测定LVSP、LVEDP、HR、±dp／dt_(max)、t-dp／dt_(max)；股动脉插管测定SBP、DBP和MAP。2、结扎大鼠冠脉左前降支，缺血30分钟后剪断结扎线造成在体心肌缺血再灌注模型，经股静脉给药。测定再灌注60分钟后血清中CK、LDH、SOD、GSH-Px和MDA含量。3、采用Langendorff离体心脏灌流法，全心停灌15分钟后再灌流造成离体心肌缺血再灌注模型，通过动脉套管侧管给药。测定再灌注30分钟后，灌流液中CK、LDH、SOD、GSH-Px和MDA含量；同时测定离体心脏冠脉流量、心肌收缩幅度和心率。结果：1、滇丹参、甘西鼠尾、褐毛甘西鼠尾可以减轻急性心肌缺血引起的LVSP、±dp／dt_(max)和t-dp／dt_(max)的降低和LVEDP的升高，对HR、SBP、DBP和MAP的影响无显著性。2、滇丹参、甘西鼠尾、褐毛甘西鼠尾可以显著降低在体心肌缺血再灌注后血清CK、LDH和MDA含量，升高血清SOD和GSH-Px活力。3、滇丹参、甘西鼠尾、褐毛甘西鼠尾可以对抗离体大鼠心脏停灌后再灌注引起的冠脉流量、心肌收缩幅度和心率的降低；降低灌流液中CK、LDH和MDA含量，提高SOD和GSH-Px的活力。结论：
滇丹参、甘西鼠尾、褐毛甘西鼠尾能改善急性心肌缺血引起的血流动力学
异常;对在体和离体缺血/再灌注引起的心肌损伤具有保护作用。
Objective: To observe the effects of Salvia yunnanensis C.H.Wright, Salvia przerwalskii Maxim and Salvia przewalsk Maxim var mandarinorum stib in hemodynamic abnormality induced by myocardial ischemia and their protective effects in myocardial ischemia/ reperfusion in rat. Methods: 1.After injecting the drugs though the femoral vein, we have examined LVSP, LVEDP, HR, ±dp/dtmax,t-dp/dtmax, HR, SBP, DBP and MAP in the model of ligating left anterior descending coronary artery (LAD) in rats; 2.We made the model of myocardia ischemia/reperfusion injury in rat by ligating the LAD for 30 minutes and followed reperfusion 60 minutes. The concentration of CK, LDH, SOD, GSH-Px and MDA in plasm were tested. 3.Via the Langendorff heart reperfused model, 5 mintutes after used the drugs, we have made the rat's heart ischemia for 15 minutes and reperfusion for 30 minutes. During the whole process, we exanined the flow of coronary artery, degree of myocardial contraction, heart rate and the concentration of the CK, LDH, SOD, GSH-Px and MDA in perfusion liquid. Results: Salvia yunnanensis C.H. Wright, Salvia przerwalskii Maxim, Salvia przewalskii Maxim var mandarinorum stib can alleviate the depress of LVSP, ±dp/dtmax, t-dp/dtmax and the increase of LVEDP. But the obviously effects on heart rate , SBP, DBP and MAP have not observed.All the treatment groups in doseage of 4g/kg can decrease the concentration of CK, LDH and MDA, and can heighten the concentration of SOD and GSH-Px in plasm after acute
myocardial ischemia/reperfusion. In the model of Langendorff heart perfused, the flow of coronary artery, degree of myocardial contraction, heart rate of the treatment groups are obviously higher compared with the untreatment group. The concentration of the CK, LDH and MDA decreased and that of SOD and MDA rised. Conclusion: Salvia yunnanensis C.H.Wright, Salvia przerwalskii Maxim, Salvia przewalskii Maxim var mandarinorum stib can ameliorate the abnormality of the hemodynamics and have the cardioprotective effects in myocardial ischemia/reperfusion in rat hearts.
滇丹参、甘西鼠尾、褐毛甘西鼠尾能改善急性心肌缺血引起的血流动力学
异常;对在体和离体缺血/再灌注引起的心肌损伤具有保护作用。
Objective: To observe the effects of Salvia yunnanensis C.H.Wright, Salvia przerwalskii Maxim and Salvia przewalsk Maxim var mandarinorum stib in hemodynamic abnormality induced by myocardial ischemia and their protective effects in myocardial ischemia/ reperfusion in rat. Methods: 1.After injecting the drugs though the femoral vein, we have examined LVSP, LVEDP, HR, ±dp/dtmax,t-dp/dtmax, HR, SBP, DBP and MAP in the model of ligating left anterior descending coronary artery (LAD) in rats; 2.We made the model of myocardia ischemia/reperfusion injury in rat by ligating the LAD for 30 minutes and followed reperfusion 60 minutes. The concentration of CK, LDH, SOD, GSH-Px and MDA in plasm were tested. 3.Via the Langendorff heart reperfused model, 5 mintutes after used the drugs, we have made the rat's heart ischemia for 15 minutes and reperfusion for 30 minutes. During the whole process, we exanined the flow of coronary artery, degree of myocardial contraction, heart rate and the concentration of the CK, LDH, SOD, GSH-Px and MDA in perfusion liquid. Results: Salvia yunnanensis C.H. Wright, Salvia przerwalskii Maxim, Salvia przewalskii Maxim var mandarinorum stib can alleviate the depress of LVSP, ±dp/dtmax, t-dp/dtmax and the increase of LVEDP. But the obviously effects on heart rate , SBP, DBP and MAP have not observed.All the treatment groups in doseage of 4g/kg can decrease the concentration of CK, LDH and MDA, and can heighten the concentration of SOD and GSH-Px in plasm after acute
myocardial ischemia/reperfusion. In the model of Langendorff heart perfused, the flow of coronary artery, degree of myocardial contraction, heart rate of the treatment groups are obviously higher compared with the untreatment group. The concentration of the CK, LDH and MDA decreased and that of SOD and MDA rised. Conclusion: Salvia yunnanensis C.H.Wright, Salvia przerwalskii Maxim, Salvia przewalskii Maxim var mandarinorum stib can ameliorate the abnormality of the hemodynamics and have the cardioprotective effects in myocardial ischemia/reperfusion in rat hearts.
引文
[1]腾艳芬．王峥涛，余国奠．丹参的药用资源研究进展．中国野生植物资源
[2]肖小河，方清茂，夏文娟，等．药用鼠尾草属数值分类与丹参药材地道性．植物资源与环境 1997；6(2)：17-21
[3]薛明，史彦斌，崔颖，等．甘西鼠尾草化学成分的研究．天然产物研究与开发 1999；12(6)：27—31
[4]陈维洲．丹参的药理．药学学报 1984；19(11)：876—880
[5]杨卫东，朱鸿良，赵保路．丹参的氧自由基清除作用．中国药理学通报 1990；6(2)：118—121
[6]杨春欣．丹参素的药理研究进展．中国药理学通报 1997；13(4)：298—301
[7]罗建详，曾凡婷，王化昌，等．丹参注射液的工艺改革．中草药通讯 1979；3：16—17
[8]徐叔云，卞如濂，陈修．药理实验方法学，北京，人民卫生出版社，2002年第三版：976—1059
[9]王进，李青，阚启明，等．氧化苦参碱的血流动力学．沈阳药科大学学报 2000；17(2)：140—141
[10]邓汉武．大鼠心肌缺血再灌注损伤实验法．中国药理学通报 1989；5(5)：317—320
[11]徐凤芹，史大卓，陈可冀，等．精制血府胶囊对犬心肌心肌缺血心脏血流动力学和心肌耗氧量的影响．中国中西医结合杂志 1998；18(1)：32—34
[12]周建政，肖文彬，等．绞股蓝总甙和人参总甙对大鼠急性心肌缺血心脏舒张功能保护作用的比较．中国药学杂志 1996；31(4)：207—210
[13]李云田．等容血液稀释和维拉帕米对缺血再灌注心肌的保护．河南医科大学学报 1997；32：84—88
[14]付润芳，冯国清，刘洁，等．前列腺素E1、川芎嗪和用大鼠心肌缺血再灌注损伤的保护作用．中国药理学通报 1998；14(6)：548—550
[15]吴斯文．氧自由基与心肌缺血再灌注损伤．《国外医学》麻醉学与复苏分册 1996；17(1)：33—36
[16]罗晓泼，刘立英，陈修．钙、自由基、前列环素及其类似物与心肌缺血再灌注损伤．中国药理学通报 1992；8(3)：174—176
[17]张洁，曾晓荣，杨艳，等．丹参酮ⅡA磺酸钠对原代培养猪冠脉平滑肌ATP敏感钾通道、钙激活钾通道的影响．泸州医学院学报 2000；23(3)：177—179
[18]费丽萍，李进禧，郑道声，等．丹参酮ⅡA磺酸钠对红细胞内游离钙浓度的影响．微循环血杂志 1997；7(4)：17—19
[19]闫彩珍，李惠兰，张荣平，等．滇丹参、甘西鼠尾、褐毛甘西鼠尾对离体豚鼠心脏的影响．昆明医学院学报 2002；23(1)
[20]闫彩珍．滇丹参、甘西鼠尾、褐毛甘西鼠尾药效学研究．昆明医学院硕士研究生学位论文 2001；6
[21]何洪静．滇丹参、甘西鼠尾、褐毛甘西鼠尾注射液对大鼠血液流变性、血栓形成及微循环的影响．昆明医学院硕士研究生学位论文 2002；6
[2]肖小河，方清茂，夏文娟，等．药用鼠尾草属数值分类与丹参药材地道性．植物资源与环境 1997；6(2)：17-21
[3]薛明，史彦斌，崔颖，等．甘西鼠尾草化学成分的研究．天然产物研究与开发 1999；12(6)：27—31
[4]陈维洲．丹参的药理．药学学报 1984；19(11)：876—880
[5]杨卫东，朱鸿良，赵保路．丹参的氧自由基清除作用．中国药理学通报 1990；6(2)：118—121
[6]杨春欣．丹参素的药理研究进展．中国药理学通报 1997；13(4)：298—301
[7]罗建详，曾凡婷，王化昌，等．丹参注射液的工艺改革．中草药通讯 1979；3：16—17
[8]徐叔云，卞如濂，陈修．药理实验方法学，北京，人民卫生出版社，2002年第三版：976—1059
[9]王进，李青，阚启明，等．氧化苦参碱的血流动力学．沈阳药科大学学报 2000；17(2)：140—141
[10]邓汉武．大鼠心肌缺血再灌注损伤实验法．中国药理学通报 1989；5(5)：317—320
[11]徐凤芹，史大卓，陈可冀，等．精制血府胶囊对犬心肌心肌缺血心脏血流动力学和心肌耗氧量的影响．中国中西医结合杂志 1998；18(1)：32—34
[12]周建政，肖文彬，等．绞股蓝总甙和人参总甙对大鼠急性心肌缺血心脏舒张功能保护作用的比较．中国药学杂志 1996；31(4)：207—210
[13]李云田．等容血液稀释和维拉帕米对缺血再灌注心肌的保护．河南医科大学学报 1997；32：84—88
[14]付润芳，冯国清，刘洁，等．前列腺素E1、川芎嗪和用大鼠心肌缺血再灌注损伤的保护作用．中国药理学通报 1998；14(6)：548—550
[15]吴斯文．氧自由基与心肌缺血再灌注损伤．《国外医学》麻醉学与复苏分册 1996；17(1)：33—36
[16]罗晓泼，刘立英，陈修．钙、自由基、前列环素及其类似物与心肌缺血再灌注损伤．中国药理学通报 1992；8(3)：174—176
[17]张洁，曾晓荣，杨艳，等．丹参酮ⅡA磺酸钠对原代培养猪冠脉平滑肌ATP敏感钾通道、钙激活钾通道的影响．泸州医学院学报 2000；23(3)：177—179
[18]费丽萍，李进禧，郑道声，等．丹参酮ⅡA磺酸钠对红细胞内游离钙浓度的影响．微循环血杂志 1997；7(4)：17—19
[19]闫彩珍，李惠兰，张荣平，等．滇丹参、甘西鼠尾、褐毛甘西鼠尾对离体豚鼠心脏的影响．昆明医学院学报 2002；23(1)
[20]闫彩珍．滇丹参、甘西鼠尾、褐毛甘西鼠尾药效学研究．昆明医学院硕士研究生学位论文 2001；6
[21]何洪静．滇丹参、甘西鼠尾、褐毛甘西鼠尾注射液对大鼠血液流变性、血栓形成及微循环的影响．昆明医学院硕士研究生学位论文 2002；6