阿霉素诱导的心脏毒性与室性心律失常易感性的研究  

Study on the Cardiotoxicity and Ventricular Arrhythmia Susceptibility Induced by Doxorubicin

作　　者：许倩倩 卫晓红 代倩倩 姜慧茹 张华敏[1] 商洪才[2,3] XU Qianqian;WEI Xiaohong;DAI Qianqian;JIANG Huiru;ZHANG Huamin;SHANG Hongcai(Institute of Basic Theory for Chinese Medicine,China Academy of Chinese Medical Sciences,Beijing 100700,China;Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing,Dongzhimen Hospital,Beijing University of Chinese Medicine,Beijing 100700,China;Dongfang Hospital,Beijing University of Chinese Medicine,Beijing 100078,China)

机构地区：[1]中国中医科学院中医基础理论研究所,北京100700 [2]北京中医药大学东直门医院中医内科学教育部和北京市重点实验室,北京100700 [3]北京中医药大学东方医院,北京100078

出　　处：《中国中医基础医学杂志》2025年第4期615-620,共6页JOURNAL OF BASIC CHINESE MEDICINE

基　　金：国家科技重大专项(2023ZD0502700,2023ZD0502705);中央高校基本科研业务费专项(2024-JYB-JBZD-046);北京市通州区2023年度医药健康产业发展项目(JX2023YJ024)。

摘　　要：目的评估阿霉素诱导大鼠急性心脏毒性后室性心律失常易感性的发生情况。方法20只SD大鼠随机分为空白组和阿霉素组,每组10只,空白组腹腔注射0.9%氯化钠溶液,阿霉素组腹腔单次注射15mg/kg阿霉素诱导急性心脏毒性。观察两组大鼠的一般状况;应用超声心动图和HE染色检测大鼠心脏功能和心肌组织的病理变化;采用电生理方法检测大鼠的心内电生理指标和室颤阈值变化;ELISA试剂盒检测大鼠血清中肌酸激酶同工酶(CK-MB)和心肌肌钙蛋白T(cTnT)的含量;TUNEL免疫荧光检测大鼠心肌组织的细胞凋亡情况。结果与空白组比较,阿霉素组大鼠左室射血分数(LVEF)、左室短轴缩短率(LVFS)显著降低(P<0.01);心内电生理结果提示,与空白组比较,阿霉素组大鼠的心率(HR)、QTc间期、P波幅度、R波幅度、QRS间期、QT间期和ST段幅度均发生显著变化(P<0.05),而PR间期、Q波幅度、S波幅度、T波幅度差异无统计学意义,心电图上P波消失,出现间距不等、大小不一的f波,RR间期不一致。通过心脏电刺激诱导室颤,与空白组比较,阿霉素组大鼠室颤阈值显著降低(P<0.01),空白组在20V时诱导出室颤,而阿霉素组在5V即可诱导出室颤;ELISA检测结果显示,与空白组比较,阿霉素组大鼠CK-MB和cTnT的含量显著增加(P<0.05);HE染色和TUNEL染色结果表明,与空白组比较,阿霉素组大鼠心肌组织结构排列紊乱,心肌细胞凋亡显著增加(P<0.05)。结论阿霉素诱导大鼠急性心脏毒性后,心功能减退,心肌损伤加剧,室性心律失常易感性增加,室颤阈值降低。Objective To evaluate the occurrence of susceptibility to ventricular arrhythmia after doxorubicin(DOX)-induced acute cardiotoxicity in rats.Methods Twenty Sprague-Dawley rats were randomly divided into a blank group(Control)and a DOX group,with 10 rats in each group.The Control group was intraperitoneally injected with 0.9%sodium chloride solution,and the DOX group was intraperitoneally injected with 15mg/kg DOX for once to induce acute cardiotoxicity.The general condition of rats in the two groups was observed.Echocardiography and HE staining were used to detect the changes in cardiac function and myocardial tissue pathology of rats.Electrophysiological methods were used to detect the changes in intracardiac electrophysiological indexes and ventricular fibrillation threshold of rats.ELISA kits were used to detect the contents of CK-MB and cTnT in the serum of rats.TUNEL immunofluorescence was used to detect the apoptosis of cells in the myocardial tissue of rats.Results Compared with the Control group,the LVEF and LVFS of rats in the DOX group were significantly reduced(P<0.01).The results of intracardiac electrophysiology suggested that compared with the Control group,the heart rate(HR),QTc interval,P wave amplitude,R wave amplitude,QRS duration,QT interval,and ST segment amplitude of rats in the DOX group all changed significantly(P<0.05),while there was no statistical significance in PR interval,Q wave amplitude,S wave amplitude,and T wave amplitude.On the electrocardiogram,the P wave disappeared and f waves with unequal spacing and different sizes appeared,and the RR intervals were inconsistent.Ventricular fibrillation was induced by cardiac electrical stimulation.Compared with the Control group,the ventricular fibrillation threshold of rats in the DOX group was significantly reduced(P<0.01).Ventricular fibrillation was induced in the Control group at 20 V,while ventricular fibrillation could be induced in the DOX group at 5 V.The results of ELISA detection showed that compared with the Control group,the co

关 键 词：阿霉素 心脏毒性 室性心律失常 室颤阈值 

分 类 号：R285.5[医药卫生—中药学]