【作者】 陶有青；

【导师】 杨传华；

【作者基本信息】 山东中医药大学 ， 中医内科学， 2012， 博士

【摘要】 目的1.复制山羊急性应激性快速性心律失常模型，开展快律宁（以下简称为KLN）胶囊抗应激性室性心律失常实验研究。2.开展KLN胶囊抗快速性心律失常药效学评价，为KLN胶囊的临床及研发工作提供实验依据。方法将实验动物分别随机分为模型对照组、阳性对照组和KLN高、中、低剂量组。1.进行山羊急性应激性心律失常模型制作的探索性研究，采用普通心电图和动态心电图相结合方式，观察山羊应激前后心率、心律失常等相关指标，进行KLN胶囊抗山羊应激性心律失常的疗效观察。2.建立氯化钡、乌头碱诱发大鼠心律失常模型和哇巴因诱发豚鼠心律失常模型，分别观察KLN胶囊抗这三种模型心律失常的出现时间、持续时间及所需氯化钡等药物的剂量。结果1.通过山羊应激模型制作的研究，仅发现窦性心动过速伴不齐，未能出现室早等室性心律失常；KLN胶囊对急性应激性窦性心动过速模型具有明显的减慢心率的作用，与模型对照组比较具有显著差异（P＜0.01）；其中KLN高、中剂量组及美托洛尔组干预后的心率已接近正常值。2.与模型对照组比较，KLN胶囊能推迟三种模型心律失常发生时间，缩短持续时间，并相应地增加心律失常出现时的所需氯化钡等药物剂量；与普罗帕酮组比较，KLN胶囊高、中剂量总体疗效相当，低剂量组疗效有显著差异（P＜0.01）；KLN各剂量组内疗效比较，高、中剂量组差异无统计学意义（P＞0.05），两者均明显优于低剂量组（P＜0.01）。结论1.根据已报道的文献研究方法，通过严格的模型复制及改良方案，尚不能制作出山羊急性应激性室性心律失常模型。2.KLN胶囊具有抗山羊应激性窦性心动过速的作用，具有剂量依赖性。3.KLN胶囊具有抗氯化钡、乌头碱、哇巴因诱发大鼠、豚鼠心律失常的作用，且具有量效关系。更多还原

【Abstract】 Objective First， copy goat acute stress tachyarrhythmia model, to carry outexperimental study of KLN capsules’ against stress-induced ventricular arrhythmiasfunction.Second，To carry out the KLN capsule anti-tachyarrhythmia pharmacodynamicevaluation, to provide experimental basis for clinical and research work of the KLNcapsule.Methods The experimental animals were randomly divided into model group, thepositive control group and the KLN high, medium and low-dose group. First，Carry outexploratory research on model of goat acute stress arrhythmias using both normal ECG andHolter. Observe the goats’ heart rate，arrhythmias and other relevant indicators before andafter stress. And do the effective observation of KLN capsule on anti-stress-inducedarrhythmias on goats. Second， To establish barium chloride, aconitine induced ratarrhythmia model and wow bar-induced guinea pig arrhythmia model, and observe theduration, the required barium chloride and other drugs dose of these three models.Results First，After the study of the goat model of stress, only sinus tachycardia witharrhythmia were found, but ventricular premature beats and other ventricular arrhythmiasfailed; the KLN capsule can significantly reduce heart rate on sinus tachycardia model ofacute stress, has significant difference (P <0.01) compared with the model group. After theintervention of KLN high, medium dose group and the metoprolol group, the heart rate hasbeen close to normal. Second，Compared with model group, the KLN capsule delayedthree models arrhythmia time, shorten the duration, and a increase in the dose of therequired barium chloride and other drugs appear. Compared with propafenone group, KLN capsule high dose and medium dose has the same overall efficacy. There are significantdifferences in the efficacy of low-dose group (P <0.01). Compare each KLN group,high-dose and medium dose group have no significant difference (P>0.05), both of whichsignificantly better than the low dose group (P <0.01).Conclusion First，According to the reported literature, through a rigorous replicationof the model and improvement programs, yet can not produce goat acute stress-inducedventricular arrhythmia models.Second，KLN capsule is effective on goat stress-induced sinus tachycardia，with thedose-effect relationship.Third，KLN capsule is effective on anti-barium chloride，aconitine，and ouabaininduced arrhythmias in guinea pigs and rats，and has a significant dose-effect relationship.更多还原