环维黄杨星D对麻醉犬急性心肌梗死的保护作用(英文)

Cardioprotective effects of Cyclovirobuxine D on the myocardial infarction in anesthetized dogs

目的 研究环维黄杨星D(CD)对犬急性心肌梗死模型的血流动力学影响和对心肌的保护作用。方法 阻断犬左冠状动脉前降支 (LAD) 6h ,记录缺血前和缺血 6h内的血流动力学和生物化学指标的变化。然后通过TTC染色测定心肌梗死面积。结果 心肌缺血前 10min静脉灌注CD对心脏血流动力学无明显影响 ,但CD可明显抑制心肌梗死后左心室压力上升最大速率 (LVdp/dtmax)、平均动脉压 (MAP)和心肌耗氧量指数 (RPP)的降低。CD明显缩小心肌梗死面积 ,对照组心肌梗死面积占缺血面积比 (IS/ARR)为 (85 .4± 9.2 ) % ;CD 0 .15mg/kg、0 .3mg/kg和 0 .6mg/kg组分别为 (5 1.2± 13.2 ) %、(46 .6± 14.3) %、(5 8.4± 8.8) % ,P <0 .0 1。CD明显降低缺血后血清CK(肌酸激酶 ) ,LDH(乳酸脱氢酶 ) ,FFA(游离脂肪酸 )和MDA(丙二醛 )水平 ,并提高血清SOD(超氧化物歧化酶 )活性 ,但CD0 .15mg/kg组降低CK作用明显强于 0 .3mg/kg和 0 .6mg/kg组。结论 CD静脉给药具有明显的心肌保护作用 ,此作用不依赖于心脏血流动力学的影响 ,CD小剂量的心肌缺血保护作用优于大剂量。其保护心肌缺血作用可能与抑制脂质过氧化 。

Objective To study hemodynamics and cardioprotective effects of cyclovirobuxine D (CD) in a canine model of acute coronary occlusion. Methods The left anterior descending coronary artery (LAD) of canine was occluded for 6 hours,hemodynamics and biochemical assays were obtained before and during 6 hours of ischemia; then, the myocardial infarct size/ischemic area at risk (IS/ARR) was assayed through triphenyltetrazolium chloride (TTC) staining. Results CD was administered intravenously 10 min before occlusion. Although there were no effects on hemodynamics after drug infusion in CD groups, CD significantly inhibited the decrease of the maximal first derivative of LVP (LVdp/dtmax), mean arterial pressure (MAP) and rate-pressure product (RPP) after myocardial infarction. CD significantly limited myocardial infarct size compared with that of vehicle (percentage of the area at risk: vehicle,85.4%±9.2%; CD 0.15mg/kg, 51.2%±13.2% ; CD 0.3mg/kg, 46.6%±14.3% ; CD 0.6mg/kg, 58.4%±8.8%; P <0.01 vs vehicle). CD inhibited the increase of serum creatine phosphokinase (CK), lactate dehydrogenase (LDH), free fatty acid (FFA) and malondialdehyde (MDA) levels and the decrease of serum superoxide dismutase (SOD) level very greatly after ischemia. The effect of CD administered at 0.15mg/kg on reducing CK was better than at 0.3mg/kg and 0.6mg/kg.Conclusion CD possesses a marked cardioprotective effect which were not dependent on changing hemodynamics. CD administered at lower dose have better cardioprotective effects than at higher dose. The inhibition of lipid-peroxidation and the clearance of free radicals probably contribute to the cardioprotective effect of CD against ischemia injury in vivo .