附子总碱及其模拟炮制品对大鼠离体心脏的毒性作用

Toxic Effect of Total Alkaloids and Simulation-Processed Product of Aconitine Radix in Isolated Hearts of Rats

目的:研究附子总碱及其模拟炮制品对大鼠离体心脏的毒性作用,探讨其作用机制。方法:建立SD大鼠的Langendorff离体心脏灌注模型。用附子总碱及其模拟炮制品的不同炮制时间点(0,20,40,60,80,120 min)炮制品以及不同累积给药剂量(0,50,100,150,300μg)对灌注模型进行干预,以左心室收缩压(left ventricular systolic pressure,LVSP),左心室舒张末期压(left ventricular end-diastolic pressure,LVEDP),左心室舒张压(left ventricular developed pressure,LVDP),左心室内压最大上升速率(+dp/dt),左心室内压最大下降速率(-dp/dt)等血流动力学参数以及心率(heart rate,HR)为指标,观察附子总碱及其模拟炮制品对大鼠离体心脏的影响。结果:与给药前平衡比较,模拟炮制80 min组累积给药100μg时显示心脏毒性,炮制100,120 min组累积给药300μg时才出现毒性(P<0.05)。附子总碱及其模拟炮制品都能增加心率,都能使LVSP,LVDP,±dp/dt明显降低,并且与累积给药量呈正相关趋势,同时使LVEDP上升。结论:附子总碱及其模拟炮制品对大鼠离体心脏均呈现出毒性作用,随炮制时间的延长,毒性下降。

Objective： To explore the toxic effects of total alkaloids and the simulation-processed product of Aconitine Radix in isolated hearts of rats. Method： Langendorff＇s heart perfusion models of SD rats were established to observe the effects of the drugs. Total alkaloids of Aconitine Radix and its simulation-processed products treated at different time points（0,20,40,60,80,120 min） and different doses（0,50,100,150,300 μg） were adopted to intervene the perfusion model. The hemodynamics parameters were observed,including left ventricular systolic pressure（LVSP）,left ventricular end-diastolic pressure（LVEDP）,left ventricular developed pressure（LVDP）,intraventricular pressure maximum upstroke velocity（＋ dp/dt）,intraventricular pressure maximum decrease velocity（-dp/dt） and heart rate（HR）. Result： Compared with the 0 min group,the 80 min simulation processing group showed cardiac toxicity at the dose of 100 μg,and 100 min and 120 min simulation processing groups showed cardiac toxicity at the dose of 300 μg（P 0. 05）. Both total alkaloids and simulation-processed products of Aconitine Radix can increase HR,significantly decrease LVSP,LVDP,± dp/dt,and increase LVEDP at the same time,with positive correlation with accumulated dosage. Conclusion： Both total alkaloids and simulation-processed products of Aconitine Radix show heart toxicity,which declines with the extension of the processing time.