光学标测技术评价乌头碱心脏毒性的剂量关系  

Optical Mapping Technology to Evaluate the Dose Relationship of Aconitine Cardiotoxicity

作　　者：张翠涵 沈长虹 冉倩 孙晨[1] 程芳 姚子晴 张若琪[1] ZHANG Cuihan;SHEN Changhong;RAN Qian;SUN Chen;CHENG Fang;YAO Ziqing;ZHANG Ruoqi(College of Pharmacy,Chengdu University of Traditional Chinese Medicine,State Key Laboratory of Southwestern Chinese Medicine Resources,Chengdu 611137,China)

机构地区：[1]成都中医药大学药学院,西南特色中药资源国家重点实验室,成都611137

出　　处：《中国现代应用药学》2024年第12期1631-1637,共7页Chinese Journal of Modern Applied Pharmacy

基　　金：四川省自然科学基金项目(2022NSFSC1349)。

摘　　要：目的 探究不同浓度乌头碱作用于心脏时对大鼠心脏心室电生理的影响。方法 利用光学标测技术,通过体外给药乌头碱0.3、1、3 ng·mL^(-1),观察给药前及给药15 min后不同浓度乌头碱对大鼠心室动作电位及钙信号的影响。结果 与空白组比较,在自发和6 Hz刺激节律下,乌头碱都能浓度依赖性延缓动作电位的传导,浓度为3 ng·mL^(-1)时具有显著性差异(P<0.05或P<0.01)。与空白组比较,当乌头碱浓度为1、3 ng·mL^(-1)时,心室动作电位时程显著延长(P<0.01)。乌头碱还能增加动作电位传导的离散度(P<0.05),并且降低有效不应期与动作电位时程的比值(P<0.01)。此外,乌头碱还能浓度依赖性延缓钙信号的传导,降低钙传导的速度(P<0.05或P<0.01),增加钙传导及钙瞬变时程的离散度(P<0.05或P<0.01),降低钙信号的幅值(P<0.01)。结论 采用光学标测技术可直观地发现乌头碱通过浓度依赖性地延缓大鼠心室动作电位及钙信号的传导来诱导心律失常的发生。OBJECTIVE To explore the effects of different concentrations of aconitine on the ventricular electrophysiology of the rat heart when applied to the heart.METHODS By optical mapping technology,the effects of different concentrations of aconitine on ventricular action potential and calcium signal in rats before and 15 min after administration were observed by in vitro administration of aconitine 0.3,1,3 ng·mL^(−1).RESULTS Compared with the blank group,aconitine could be concentrationdependent to delay the conduction of action potentials under both spontaneous and 6 Hz stimulation rhythms,and there was a significant difference at a concentration of 3 ng·mL^(−1)(P<0.05 or P<0.01).Compared with blank group,when the concentration of aconitine was 1 and 3 ng·mL^(−1),the action potential duration(APD)of the ventricle was significantly prolonged(P<0.01).Aconitine could also increase the dispersion of action potential conduction(P<0.05)and reduce the ratio of effective refractory period(ERP)to APD90(P<0.01).In addition,aconitine could also be concentration-dependent delay of calcium signal conduction,reduce the speed of calcium conduction(P<0.05 or P<0.01),increase the dispersion of calcium conduction and calcium transient duration(P<0.05 or P<0.01),and reduce the amplitude of calcium signal(P<0.01).CONCLUSION Using the optical labeling technique,it can be visualized that aconitine induces arrhythmia by concentration-dependent delay of ventricular action potential and calcium signaling in rats.

关 键 词：乌头碱 光学标测 心脏毒性 动作电位 钙信号 

分 类 号：R285[医药卫生—中药学]