摘要
目的研究蟾酥注射液以及合用IL-6条件下,其潜在心律失常风险及其机理。方法采用豚鼠在体心电图以及左心室肌细胞动作电位、钙电流和钠电流实验,分析心电图心率、P-R、QRS以及QTc间期,及其变化基于的机理。结果①在体心电图表明1倍临床剂量蟾酥注射液未能引起心电图明显改变;而单独IL-6(18.4μg·kg^(-1))及合用1倍临床剂量蟾酥注射液明显引起P-R及QTc间期延长。②蟾酥注射液1倍临床浓度对动作电位复极90%水平时程(APD 90)无明显作用;而单独IL-6(20μg·L^(-1))以及合用1倍临床浓度蟾酥注射液明显延长动作电位APD 90。③蟾酥注射液1倍临床浓度对Ca^(2+)电流无明显抑制作用,而IL-6(20μg·L^(-1))合用1倍临床浓度蟾酥注射明显抑制Ca^(2+)电流。④蟾酥注射液1、5、10倍临床浓度未能明显抑制Na^(+)电流;IL-6(20μg·L^(-1))及合用蟾酥注射液对Na+电流无明显作用。结论蟾酥注射液临床上使用存在低心律失常风险,但患者存在以IL-6增加为特征的炎症条件下,IL-6加重蟾酥注射液对Ca^(2+)电流的抑制作用,导致房室传导阻滞的风险明显增加。
Aim To explore the arrhythmic risk of Chan Su intravenous injection(CS)and its underlying mechanismin in the absent or presence of IL-6.Methods The recording techniques of guinea pig in vivo ECG,the action potential,L-type Ca^(2+) and Na^(+) currents from left ventricular myocytes were used to analyze heart rate(HR),P-R,QRS and QTc intervals and the underlying mechanism.Results①CS at one time CRD(clinically relevant dose)insignificantly changed the guinea pig in vivo ECG.However,the IL-6(18.4μg·kg^(-1))only and the combinational use of IL-6(18.4μg·kg^(-1))plus CS(one time CRD)remarkably prolonged the P-R and QTc intervals.②The CS at one time CRC(clinically relevant concentration)had no significant change in the action potential duration at 90%repolarization level(APD_(90)).The IL-6(20μg·L^(-1))only and the combination of CS at one time CRC plus IL-6(20μg·L^(-1))significantly prolonged APD_(90).③Moreover,the IL-6(20μg·L^(-1))combined with CS at one time CRC significantly inhibited the L-type Ca^(2+)current.④CS at one,five,ten time CRC,IL-6(20μg·L^(-1))alone and IL-6(20μg·L^(-1))combined with CS had no significant effects on Na+current.Conclusions CS intravenous injection has low risk of arrhythmia in the clinical settings.However,in presence of high titer of IL-6 characterized by inflammation,CS may induce the atrioventricular conduction block due to the blockade effect on Ca^(2+)current by both of CS and IL-6.
作者
高倩雯
肖钰洁
王羽维
朱晓佳
刘福明
陈可塑
王荣荣
陈龙
GAO Qian-wen;XIAO Yu-jie;WANG Yu-wei;ZHU Xiao-jia;LIU Fu-ming;CHEN Ke-su;WANG Rong-rong;CHEN Long(Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica,School of Pharmacy,Nanjing University of Chinese Medicine,Nanjing 210023,China;Jiangsu Province Hospital of Chinese Medicine,Affiliated Hospital of Nanjing University of Chinese Medicine,Nanjing 210029,China;Medical School of Nanjing University,Nanjing 210093,China;Institute of Chinese Medicine of Taizhou China Medical City,Taizhou,Jiangsu 225300,China)
出处
《中国药理学通报》
CAS
CSCD
北大核心
2022年第5期712-718,共7页
Chinese Pharmacological Bulletin
基金
江苏省“六大人才高峰”(No TD-SWYY-069)
江苏省科技计划(社会发展-面上项目)(No SEB2020740365)。
关键词
蟾酥注射液
IL-6
心律失常
动作电位
钙通道
钠通道
ChanSu intravenous injection
IL-6
arrhythmia
action potential
Ca^(2+) channel
Na^(+) channel