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槐定碱抗心律失常作用及其机理

The antiarrhythmic effects and mechanisms of sophoridine

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【作者】 崔利华张宝恒

【Author】 CUI Li-hua, ZHANG Bao-heng(Dept of Pharmacology, College of Basic Medical Science, Beijing Medical University, Beijing 100083)

【机构】 北京医科大学基础医学院药理教研室北京医科大学基础医学院药理教研室 北京 100083北京 100083

【摘要】 槐定碱(Sop)明显对抗由乌头碱、BaCl2、CaCl2、肾上腺素和哇巴因诱发的心律失常,提高家兔左心室电致颤阈。Sop减慢大鼠和家兔的正常心率,延长P-R和校正Q-T间期;减慢离体家兔右心房自发频率。Sop使异丙肾上腺素加速离体心房自发频率的量效曲线右移并抑制最大反应。Sop 40μM使离体豚鼠心室乳头肌细胞动作电位零相去极化最大上升速率Vmax明显减慢,有效不应期(ERP)和动作电信时程(APD)显著延长。提示Sop具有奎尼丁样作用,阻滞钠通道是其抗心律失常的主要作用机理。

【Abstract】 The effects of sophori-dine(Sop) on experimental arrhythmias in animals and its mechanisms were studied. Sop is an alkaloid isolated from Sophora alopecuroids Linn., a traditional Chinese herb. The iv LD50 of Sop in mice was 54.4±1.0mg/kg。The results showed that Sop had significant effects on different experimental models of arrhythmia. Sop(11 mg/kg iv) could markedly reduce or arrest the arrhythmia induced by aconitine (12μg/kg iv) in rats. Pre-treatment with Sop (11 mg/kg for rats and 5 mg/kg for rabbits iv) significantly shortened the duration of arrhythmias elicited by aconitine (25μg/kg iv)or by BaCl2(6 mg/kg iv) in rats and by adrenaline (0.06mg/ kg iv) in rabbits. Sop (10.4, 12.5 and 15 mg/kg iv) obviously reduced the incidence of ventricular fibrillation and mortality produced by CaCl2 (110 mg/kg iv) in rats. The doses of ouabain necessary to cause various kinds of arrhythmias and cardiac arrest in guinea pigs and the ventricular fibrillation threshold to electrical stimulation in rabbits were elevated markedly by giving Sop (15 mg/kg iv).The ECG of rabbits was significantly changed after intravenous injection of Sop 15 mg/kg. Heart rates were reduced, the P-R intervals and the corrected Q-T intervals were prolonged, but the BP was not affected. Sop (96 μM and 240 μM) depressed the spontaneously beating of the isolated right atrias of rabbits markedly.In the isolated spontaneously beating atrias of rabbits, Sop (240 and 96 μM) shifted the dose-response curves of isoprenaline to the right side and inhibited the maximum response while propranolol shifted the curve to the right parallely.In a further experiment, the effect of Sop on the affinity of β-ad-renoceptors of duck erythrocyte membrane was studied by means of radio-ligand binding assay. The result showed that Sop was quite different from (±) propranolol, it exerted no competitive inhibition on [3H] DHA specific binding with β-adrenoceptors. The electrophysiologic effects of Sop on the isolated guinea pig’s papillary muscle cells were observed by intracelluar capillary glass electrode. Thirty minutes after perfu-sion with Tyrode’s solution containing Sop 40 μM, the duration of action potential (APD) and the effective refractory period (ERP) were greatly prolonged, the ratio of ERP over APD was increased markedly and the maximum depolarization rate of phase 0 of action potential (Vmax) was obviously reduced while the resting potential (RP) remained unchanged. The results suggested that Sop was similar to quinidine which acted primarily by depressing the rapid channel for sodium conductance and this may be the most important mechanism of antiarrhy-thmic effects of Sop.

  • 【文献出处】 中国药理学与毒理学杂志 ,Chinese Journal of Pharmacology and Toxicology , 编辑部邮箱 ,1986年01期
  • 【被引频次】11
  • 【下载频次】87
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