赞丹松口服液抗心肌缺血及抗心律失常药效学研究

【作者】 王雨梅；

【导师】 王敏伟；

【作者基本信息】 沈阳药科大学 ， 药理学， 2002， 硕士

【摘要】 本文研究了蒙药赞丹松口服液(简称ZDK)的抗心肌缺血、抗心律失常作用，并对其作为口服液给药的安全性进行了考察，以期为其进一步开发成为一种治疗冠心病的新蒙药奠定理论基础。 对心肌缺血影响结果表明：ZDK以三个剂量组(高剂量为临床用量的10倍，中剂量组为临床用量5倍，低剂量组为临床等效量)对动物经口给药，能明显延长小鼠在常压缺氧条件下的存活时间；延长夹闭气管小鼠心电消失时间；缓解异丙肾上腺素所致的大鼠急性心肌缺血，增强缺血心肌的超氧化物歧化酶(SOD)活性，降低心肌丙二醛(MDA)含量；抑制垂体后叶素所致大鼠心肌缺血时T波抬高及心率的减慢；明显缩小急性心肌缺血犬心肌的梗塞区面积；增加其冠脉流量，降低冠脉阻力，改善心肌的供血供氧；减少心肌耗氧量和氧利用率，从而改善心肌缺血状况；给药后犬血清一氧化氮(NO)水平明显升高，而血浆内皮素(ET)水平显著降低。 对心律失常影响结果表明：ZDK对氯仿诱发小鼠心室纤颤(VF)有保护作用；能显著对抗氯化钡、乌头碱及冠脉结扎所致的大鼠心律失常；同时能提高电刺激诱发家兔室颤阈(VFT)。ZDK可降低300／s、100／s、30／s及3／s四个切变率下的全血粘度(BV)，全血还原粘度(RBV)，红细胞聚集指数(EAI)，红细胞刚性指数(ERI)，红细胞电泳时间(EMT)，对红细胞压积(HCT)，红细胞计数(EC)没有影响。此外可延长戊巴比妥钠所致小鼠睡眠时间。 安全性实验结果表明：ZDK小鼠最大给药量为108g／kg以上，相当沈阳药科大学硕士学位论文 摘要一于临床用量的480倍；以临床给药量的80倍给予大鼠3个月未发现毒性反应，说明毒性较低。更多还原

【Abstract】 Protective effects of arrhythmia and myocardial ischemia of Mongolia Medicine ZDK were studied, meanwhile, the safety was also described in this paper.Results of protective effects on myocardial ischemia showed that ZDK of three dosages not only prolong the mean survival time under ordinary pressure, the disappearance time of electrocardiographic sign after clamping the trachea in mice, but also obviously ameliorate acute myocardial ischemia induced by isoprenaline in rats, increase SOD activity and reduce the level of MDA on myocardium. T wave changes in ECG by pituitrin were retarded, decrease of HR was prohibited in rats. The infarct range on acute myocardial ischemia in canines was significiantly decreased. ZDK could obviously increase the coronary arterial blood flow, decrease total coronary arterial resistance.so as to improve myocrdial blood andoxygensupply.Meanwhile, ZDK had the effects on reducing utility ratio of oxygen and the amount of myocardial oxygen consumption. ZDK could increase the serum NO levels,decrease the plasma ET levels markedly in canines.The antiarrhythmic results showed that ZDK significantly decreased the incidence of VF induced by chloroform in mice and the time of VF induced by barium chloride, antagonized the arrhythmias induced by aconitine and coronary occlusion in rats . ZDK could increase the threshold of electric stimulation-induced VF in rabbits.Meanwhile,in hemorrheology study ,thedata indicated the whole blood high-shear and low-shear viscosity, whole blood reduced viscosity, erythrocyte aggregation index ,erythrocyte rigidity index,and erythrocyte emigration time were decreased. ZDK could effectively prolong the sleeping time induced by pentobarbital sodium in rats. Safety experiment showed that the largest i.g amount of ZDK were 108g/kg in mice. Safety experiment of three months in rats found no poisonous effects.更多还原