附子中乌头碱对大鼠心功能效-毒剂量关系测定

Dose-toxicity Relationship Study for Cardiotonic Effect of Aconitine

目的:动态观察乌头碱的心脏毒性与强心作用。并计算其毒理学参数与药效学参数,评价其使用的安全性,为其临床应用提供实验依据。方法:以大鼠Ⅱ导联心电图变化为指标,经大鼠股静脉缓慢恒速推注乌头碱,连续观察大鼠心电图变化,动态观察乌头碱对心脏毒性的量-毒关系;选用钙离子拮抗剂尼莫地平复制大鼠心衰模型,经大鼠股静脉缓慢恒速推注乌头碱,以心率、左心室内压最大上升速率(+dp/dtmax)和反映心脏做功的指标率压积(RPP)为指标,动态观察乌头碱的强心作用。结果:以RPP,+dp/dtmax为指标计算乌头碱的50%最大效应量(ED50),以室性早搏(PVC),停搏(CA)为指标计算乌头碱的半数中毒量(TD50)、半数致死量(LD50),则乌头碱的治疗指数(TI,按RPP计算)分别为1.84,17.22,TI(按+dp/dtmax计算)分别为1.23,11.54。结论:乌头碱具有强心作用,但也具有心脏毒性,安全范围狭窄。

Objective：To analyze the relationship between toxicity and cardiotonic effect of aconitine,calculating the therapeutic index（TI） of aconitine.Method： Regarding rat＇s electrocardiogram（ECG） change as the index,the toxicity to heart induced by aconitine was studied.Nimodipine,one of Ca2＋ antagonist,was used to make heart failure model in rats.The aconitine was injected through femoral vein continuously.The effect on heart rate,＋dp/dtmax,LVDP-rate pressure product（RPP） was observed.Result： Regarding RPP or ＋dp/dtmax as the index of ED50 and regarding PVC or CA as the index of TD50 or LD50,LD50/ED50 or TD50/ED50 was used to calculate the therapeutic index（TI） of aconitine,TI（RPP）were 1.84,17.22 and TI（＋dp/dtmax）were 1.23,11.54 respectively.Conclution： Aconitine has cardiotonic effect but has toxicity to heart.TI is small.