附子水提组分含药血清对大鼠离体心功能影响的“毒-效”关联研究

Relevance Evaluation Research about Toxicity and Efficacy of the Influence on the Rats' Cardiac Function with Medicated Serum from Aconite Water Extract

目的研究附子水提组分含药血清对大鼠离体心功能的影响,探讨附子药效和毒性的关联性。方法采用Langedorff离体心脏灌流实验,分别观察附子药典规定剂量和大剂量含药血清对大鼠离体心脏心输出量、心肌收缩力和心率的影响。结果药典规定剂量下的附子含药血清能够明显增加离体心的心输出量和心肌收缩力,增加幅度呈现明显的剂量依赖性;大剂量下的附子含药血清可以增加心输出量和心肌收缩力,但在4.28 g·kg-1及以上的剂量下,增加幅度变小,不随剂量升高而继续加大;所有剂量下对心率的影响没有出现显著性差异。结论药典规定剂量下附子水提组分在能够明显增强离体心功能,呈现一定"量-效"关系;大剂量下离体心脏功能随剂量的增大表现出心肌收缩力量不足,心输出量减少的毒副作用,呈现一定的"量-毒"关系。因此,必须重视大剂量应用附子时的毒副作用检测工作,研究药效发挥和毒性表达的关联性,找到一个合理有效的用药剂量范围,更好的为临床安全用药提供指导。

To study the influence of cardiac function with the drug serum in Aconite water extract and explore the correlation between efficacy and toxicity of Radix Aconite. Methods Take the myocardial perfusion experiment named Langedorff to observe the changes of cardiac output and myocardial contractility in isolated heart with different doses from pharmacopoeia prescribed doses to high doses. Results The cardiac output and myocardial contraction force of isolated heart could be significantly increased with the pharmacopoeia prescribed doses＂ medicated serum, and the increase amplitude was connected with doses obviously. But in large doses, the cardiac output and cardiac muscle contraction force could not be increased much more. There were no significant changes in heart rate of all doses. Conclusion Under the pharmacopoeia prescribed doses, the cardiac function of isolated heart could be increased with Aconite water extract and present a certain ＂dose-efficacy＂ relationship. But in large doses, the myocardial contraction force of isolated heart was insufficient and the cardiac output was decreased along with the increasing dose, and presented a certain ＂dose-toxicity＂ relationship. Therefore, the monitoring work of toxicity below the high doses should be paid attention to and the relevancy between efficacy and toxicity should be researched, so as to find a reasonable and effective dosage range, and to provide guidance for clinical safe drug use.