哇巴因对大鼠心脏的毒性作用分析

发布时间：2018-02-10 05:37

本文关键词： 哇巴因心律失常美托洛尔自主神经系统量效关系　出处：《山西医科大学》2017年硕士论文　论文类型：学位论文

【摘要】：目的:1.观察美托洛尔对哇巴因致大鼠心律失常作用的影响,并探讨β受体阻断剂(β-blocker)应用于洋地黄类药物中毒的相关机制;2.应用langendorff离体心脏灌流系统,对哇巴因抑制离体大鼠心脏功能的时反应量-效关系(Timed dose-response relationship,TDRR)进行了观察和分析。方法:1.应用Langendorff灌流装置进行离体心脏灌流试验,正常SD大鼠随机分成5组:正常对照组,哇巴因模型组和4、20及100μmol/L美托洛尔干预组,每组8只动物;记录给入哇巴因后固定时间内各组自主发生的室性期前收缩PVB数目,室速及室颤的发生率,记录时间为60分钟。2.在体麻醉实验使用股静脉注射给药,正常SD大鼠随机分为5组:正常对照组,哇巴因模型组,和0.4mg/kg、2mg/kg、10mg/kg美托洛尔干预组,每组8只动物;观察出现各种心律失常(VP、VT、BBB、VF)及心脏停搏(CA)出现的时间,并计算出现上述现象时哇巴因的累计用量。3.利用Langendorff灌流装置进行离体心脏灌流试验,用台式灌流液将哇巴因配置为3μmol/L、10μmol/L、30μmol/L、100mol/L、300mol/L、1000mol/L的6个浓度组,记录各浓度组左侧心室发展压(LVDP)和左侧心室舒张末压力(LVEDP)的变化曲线,记录时间为30分钟。结果:1.离体心脏灌流实验中,统计60min内各组的室性期前收缩(PVB)数目,室速(VT)、室颤(VF)发生率,未发现美托洛尔干预组与哇巴因模型组在心律失常各指标之间存在显著差异(P0.05);2.在体麻醉动物实验中,应用美托洛尔后可延长哇巴因致室性心律失常(二联律、短阵及持续性室性心动过速)出现的时间,但哇巴因致传导阻滞(束支阻滞及房室阻滞)的时间提前,室颤发生率显著减少,动物存活时间延长。3.在对收缩功能的分析中发现哇巴因随着浓度的升高(3~1000μmol/L),左心室发展压(LVDP)抑制率增大,潜伏期缩短,达峰时间在低浓度(30μmol/L)延长而高浓度(100μmol/L)缩短,平均抑制速率加快;在对舒张功能的分析中发现哇巴因随着浓度的升高(3~1000μmol/L),左室舒张末压(LVEDP)最大升高幅度增大,且随着浓度升高出现潜伏期缩短,达到峰值时间延长,平均升高速率加快等效应。结论:1.哇巴因在离体灌流心脏及在体条件下都可以稳定的诱发出心律失常,美托洛尔在离体条件下可能不发挥抗哇巴因心脏致心律失常作用,在体条件下可对抗哇巴因致室性心律失常作用,但加重哇巴因导致的传导阻滞。2.哇巴因抑制离体大鼠心脏收缩及舒张功能不仅存在着量反应量-效关系(GDRR),也存在着明确的时反应量-效关系(TDRR)。
[Abstract]:Objective 1. To observe the effect of metoprolol on arrhythmia induced by ouabain in rats, and to explore the mechanism of 尾 -blocker used in digitalis intoxication. The isolated cardiac perfusion system of langendorff was used. The time-response dose-effect relationship between ouabain and dose-response relationship in isolated rat heart was observed and analyzed. Methods: 1. Using Langendorff perfusion device, normal SD rats were randomly divided into 5 groups: normal control group. Ouabain model group and metoprolol intervention group (40 渭 mol/L and 100 渭 mol/L), 8 animals in each group, recorded the number of spontaneous ventricular premature systolic PVB, the incidence of ventricular tachycardia and ventricular fibrillation in each group during the fixed time after injection of ouabain. The recording time was 60 minutes. 2. The normal SD rats were randomly divided into 5 groups: normal control group, ouabain model group, and 0.4 mg / kg / kg 2 mg / kg metoprolol group with 8 animals in each group. To observe the time of occurrence of various arrhythmias, such as VPV, VTT, BBBV) and cardiac arrest (CAA), and to calculate the cumulative dosage of ouabain. 3. To carry out the in vitro cardiac perfusion test with Langendorff perfusion device. Ouabain was allocated to 3 渭 mol / L 10 渭 mol / L ~ 30 渭 mol / L ~ 30 渭 mol / L ~ 100 mol / L ~ 100 mol / L ~ 100 mol / L ~ 100 mol / L ~ (-1) L ~ (-1) L ~ (-1) L ~ (-1) 路L ~ (-1) 路L ~ (-1). The changes of LVDPDP) and LVEDP) of left ventricular development pressure and left ventricular end-diastolic pressure were recorded in each concentration group for 30 minutes. Results 1. In isolated heart perfusion experiment, the left ventricular end-diastolic pressure (LVDP) and left ventricular end-diastolic pressure were recorded. The number of PVB, the incidence of ventricular tachycardia (VT) and ventricular fibrillation (VF) in each group within 60 minutes were counted. There was no significant difference in arrhythmia between metoprolol intervention group and ouabain model group. Metoprolol prolonged the onset of ouabain induced ventricular arrhythmias (biphasic, short array and persistent ventricular tachycardia), but ouabain-induced block (bundle branch block and atrioventricular block) was earlier. The incidence of ventricular fibrillation was significantly reduced, and the survival time of animals was prolonged .3.The results of analysis of systolic function showed that ouabain increased the inhibition rate of LVDPs and shortened the latency with increasing concentration of ouabain at 1000 渭 mol 路L ~ (-1) 路L ~ (-1). The peak time was prolonged at low concentration of 30 渭 mol 路L ~ (-1), while 100 渭 mol / L of high concentration was shortened, and the average inhibition rate was increased. In the analysis of diastolic function, it was found that ouabain increased the maximum amplitude of left ventricular end-diastolic pressure (LVEDPP) with increasing concentration of 31000 渭 mol 路L ~ (-1) 路L ~ (-1) 路L ~ (-1) 路L ~ (-1). With the increase of concentration, the incubation period was shortened, the peak time was prolonged, and the average rate of increase was increased. Conclusion: 1. Ouabain can induce arrhythmia steadily in isolated perfused heart and in vivo. Metoprolol may not play an antiarrhythmic effect on ouabain heart in vitro, but it can antagonize the ventricular arrhythmia induced by ouabain in vivo. However, the inhibition of systolic and diastolic function of isolated rat heart by ouabain was aggravated by ouabain. There was not only a dose-response dose-effect relationship, but also a definite time-response dose-effect relationship.
【学位授予单位】：山西医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R54

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