【摘要】 目的:探讨不同煎煮时间对附子在心脏方面的功效、毒性的影响,并探索其相关机制。方法:用八木氏法进行离体蛙心灌流,运用四导生理记录仪记录其心率、左心室收缩压、左心室舒张末压、+dp/dt_max、-dp/dt_max等参数,观察不同煎煮时间、不同浓度的附子提取物对处于Ringer液及低钙Ringer液环境下蛙心的影响,同时测定其小鼠口服急性毒性作用。结果:在低钙Ringer液中:附子煎煮0.5小时在1 000原生药mg/ml浓度时,可迅速引起室性心动过速,并很快出现心力衰竭、停搏等现象,但在冲洗后可逐渐恢复正常;附子煎煮4小时在低于0.1原生药mg/ml～1 000原生药mg/ml浓度下,对离体蛙心有一定的抑制作用;附子煎煮10小时在低于100原生药mg/ml浓度下,可显著增加心内压最大上升速率和最大下降速率,增加左心室收缩压,增加心内压最大下降速率的作用最明显。附子煎煮24小时在低于0.1原生药mg/ml～1 000原生药mg/ml浓度下对离体蛙心无明显影响。在Ringer液中:附子煎煮0.5小时在100原生药mg/ml浓度时,可显著减慢心率、减慢心室内压最大上升速率和最大下降速率,其中,减慢心率及抑制心脏最大下降速度的作用最明显;而在1 000原生药mg/ml浓度时,可迅速引起室性心动过速,并迅速出现心力衰竭、停搏等现象,但在冲洗后可逐渐恢复正常;附子煎煮4小时在低于0.1原生药mg/ml～1 000原生药mg/ml浓度下,对离体蛙心有一定的抑制作用;附子煎煮10小时在低于100原生药mg/ml浓度下,对离体蛙心无明显影响,但在100原生药mg/ml浓度以上时,可显著减慢心室内压最大上升速率和最大下降速率,显著降低左心室收缩压。附子煎煮24小时在低于10原生药mg/ml浓度下,对离体蛙心无明显影响。但在10原生药mg/ml～1000原生药mg/ml浓度下,可显著增加心室内压最大上升速率和最大下降速率,增加左心室收缩压。测得小鼠口服附子0.5 h水煎液的LD₅₀为8.2415原生药g/kg,附子4h水煎液LD₅₀为183.2原生药g/kg,附子10 h水煎液、附子24 h水煎液的最大耐受量均为大于300原生药g/kg。结论:附子对心脏的毒性作用主要来源于乌头双酯型生物碱,其强心作用主要与乌头原碱等有关,其作用机理与细胞内外钙离子失衡密切相关。更多还原

【Abstract】 Objective: To explore the influences and mechanism of decocting times on the efficacy and toxicity of aconite. Methods: Isolated frog heart was perfused with Bamu’s method, parameters of frog heart rate, left ventricular systolic pressure, left ventricular end diastolic pressure, +dp/dt,-dp/dt were recorded by four-channel physiological recorder. The effects of aconite extract on Frog heart in low calcium Ringer and normal Ringer solution were observed, in different decoction time and concentrations, respectively. The acute toxicity of aconite extract in mice was determined.Results: In low calcium Ringer solution, ventricular tachycardia, heart failure and cardiac arrest were caused soon by 1000 mg/ml raw aconite decocted for 0.5 hours, but gradually returned to normal after washed. Aconite decoction under the dose of 0.1～1000 mg/ml raw drug that decocted for 4 hours caused the inhibitory effect on isolated frog heart. Aconite decoction under the dose of 100 mg/ml raw drug that decocted for 10 hours significantly increased max increasing and decreasing intracardiac pressure rates and the left ventricular pressure,the max decreasing intracardiac pressure rate showed significant difference. When the dose of Aconite was lower than 0.1～1000 mg raw drug/ml decocted for 24 hours, it showed no significant effect on the frog heart. In normal Ringer’s solution, 100 mg/ml raw drug aconite decocted for 0.5 hours significantly slowed down the heart rate and max increasing and decreasing intracardiac pressures. Aconite at the dose of 1000 mg raw drug/ml quickly caused the ventricular tachycardia,the heart failure and the cardiac arrest, but gradually returned to normal after washed. Aconite decoction under the dose of 0.1～1000 mg raw drug/ml that decocted for 4 hours caused the inhibitory effect on isolated frog heart. Aconite decoction under the dose of 100 mg raw drug/ml that decocted for 10 hours had no effect on the frog heart, while the dose of Aconite was higher than 100 mg raw drug/ml, it significantly decreased the max increasing and decreasing intracardiac pressures and LVSP. Aconite decoction under the dose of 10 mg raw drug/ml that decocted for 24 hours had no effect on the isolated frog heart. Aconite at the doses of 10～1000 mg raw drug/ml significantly decreased the max increasing and decreasing intracardiac pressures and LVSP. After oral administration of Aconite water extract, LD50 was 8.2415 g and 183.2 g raw drug/kg on 0.5 h and 4 h decoction, respectively. The max torelance doses of aconite 10 h and 24 h decoction were both higher than 300 g raw drug/kg.Conclusion: The heart toxicity of aconite is mainly caused by aconite diester alkaloid. Its cardiotonic effect is mainly caused by aconitine and the mechanism is closely related to the imbalance of intracellular and extracellular calcium ions.更多还原