【作者】 段为钢；

【导师】 李惠兰； 张荣平；

【作者基本信息】 昆明医学院 ， 药理学， 2004， 硕士

【摘要】 目的：与复方丹参注射液(丹参+三七)比较，研究三种滇产鼠尾草、滇丹参、甘西鼠尾和褐毛甘西鼠尾分别与三七合用对大鼠心肌缺血再灌注损伤的保护作用，探讨这三种滇产鼠尾草注射液在抗心肌缺血再灌注损伤方面替代丹参的可行性，探讨复方制剂的协同作用。方法：在体实验采用冠脉结扎松扎法建立大鼠心肌缺血再灌注模型(缺血30min，再灌注60min)，实验过程中以Ⅱ导联记录心电图变化，实验结束后取血清测定MDA、LDH、CK、SOD、GSH-Px，并测定心肌梗塞面积。离体实验采用Langerdoff灌流法建立心肌缺血再灌注模型，低灌(流量：0.4ml／min)15min，再灌注30min，再灌注后收集灌流液测定MDA、LDH、CK、SOD、GSH-Px。全程记录心肌收缩幅度、冠脉流量和心率。结果：1)这四种复方制剂均能显著降低在体和离体缺血再灌注后MDA、CK、LDH水平，升高SOD和GSH-Px，并有一定的剂量相关性。2)这四种复方制剂在在体模型均能加快心率，减轻ST段抬高程度，减少心肌梗塞面积；增加离体大鼠再灌注心脏的心肌收缩幅度、冠脉流量。3)与文献资料比较表明，各复方制剂在降低CK水平上强于单方制剂。4)三种滇产鼠尾草复方制剂高剂量(4g／kg)在降低在体生化指标MDA(p＜0.05，0.01)上强于复方丹参；除复方滇丹参外，各复方制剂在升高GSH-Px上优于复方丹参制剂(p＜0.05)；复方甘西鼠尾在高剂量时升高GSH-Px强于丹参(P＜0.01)。结论：丹参和三种滇产鼠尾草复方制剂均有较好的抗心肌缺血再灌注损伤作用，复方制剂优于其单方制剂，存在抗大鼠心肌缺血再灌注损伤的协同作用，三种滇产鼠尾草在抗心肌缺血再灌注损伤方面可代用丹参。其机制可能抗氧自由基损伤、钙拮抗等有关。更多还原

【Abstract】 Background: Danshen (Salvia miltiorrhiza Bunge, SM), Diandanshen (S. yunnanesis C. H. Wright, SY), Ganxishuwei (S. przewalskii Maxim., SP), Hemaoganxishuwei (S. przewalskii Maxim. Var. mandarinorum stib.), and Sanqi [Panax notoginseng (Burk.) F.H.Chen, PN] are traditional drugs, which have been used to treat cardiovascular diseases for many years in China. Objective: In order to find out the cardio protection induced by three compounded injections made from SY+PN, SP+PN, SPM+PN respectively, during ischemia/reperfusion in rats, compared with injection made from SM+PN. And to confirm the synergism of the compounded injections, and find out whether the three drugs, SY, SP, and SPM can be used as SM against cardio ischemia/perfusion injury or not. Methods: Two ischemia/reperfusion models were employed. In one mordel, we ligated rats’ artery of left anterior descending (LAD) for 30 min, then let it loose for 60 min, and we recorded the electrocardiogram (ECG) during experiment. We examined maleic dialdehyde (MDA), lactate dehydrogenase (LDH), creatine kinase (CK), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) in rats’ serum after reperfusion. In another model, a heart-perfusion model in vitro, we perfused every rat’s heart at low rate of flow with Kreb’s solution for 15min at first, then followed normal perfusion for 30min, also examined MDA, LDH, CK, SOD, and GSH-Px in the flow of effluent after reperfusion. Contractile force, perfusion flow, and rhythm were recorded during experiment. Results: 1) All the four injections were able to decrease MDA, CK, LDH, and increase SOD, GSH-Px, in a way of dose-dependence, in vivo and in vitro. 2) All the four injections were able to quicken heart rhythm, mitigate ST segment, and decrease infarcted area in vivo. And were able to alleviate contractile force during ischemia, and enhance myocardio constractile force, increase coronary flow in the state of reperfusion. 3) It was indicated that all the compounded injections decreased CK in vivo more powerfully than all the single historical ones respectively. 4) The three compounded injections of SY, SP, SPM decreased MDA at high dose (4g/kg) more powerfully than that of SM (p<0.05,0.01), in vivo; and except for SY, increased GSH-Px more powerfully than that of SM (p<0.05). In vitro, at high dose, the compounded injection of SP more powerfully increased GSH-Px than that of SM (p<0.01). Conclusion: All the three compounded injections (from SY+PN, SP+PN, and SPM+PN, respectively) employ cardio protection against ischemia/perfusion injury, and are similar to injection from SM+PN, and are more effective than the single ones respectively, which suggest that there is synergism of the compounded injections and that the three drugs can be replacer for SM to protect myocardium from ischemia/reperfusion injury. The mechanisms of which may be associated with blocking calcic channels, deactivating oxygen free radicles.更多还原