cTnT早期诊断蒽环类药物心脏毒性的实验研究

cTnT as a marker for early detection for anthracycline-induced cardiotoxicity

目的:研究血清肌钙蛋白T(cT-nT)浓度是否可以成为蒽环类药物心脏毒性早期诊断指标。方法:新西兰雄性兔44只,随机分为对照组(8只)和实验组(36只)。对照组新西兰兔注射等体积的生理盐水;实验组新西兰兔静脉注射多柔比星2 mg/(kg.次),1次/周,根据实验周数不同,实验组分为1周组(8只)、2周组(8只)、4周组(9只)和8周组(11只)。经胸超声心动图测量左室射血分数(LVEF)和左室短轴缩短分数(FS)以及E峰和A峰比值。血清GPBB浓度测量采用ELISA方法。心肌光镜Billingham评分和电镜检查评价多柔比星心脏毒性。结果:8周组新西兰兔LVEF、FS和E/A值均下降,P<0.05。与对照组相比,4周组新西兰兔血清cTnT浓度明显升高,P<0.05;8周组新西兰兔血清cTnT浓度显著高于其他组,P<0.05。光镜下4周组新西兰兔心肌损害比对照组严重,P<0.05;8周组新西兰兔心肌损害最严重,P<0.05。电镜下线粒体水肿和断裂可见于2周组、4周组和8周组,心肌损伤程度与多柔比星累积剂量有关。相关分析提示,血清cTnT浓度与多柔比星累积剂量(r=0.887,P<0.001)及血清cTnT浓度与心肌损害的程度均呈正相关,r=0.916,P<0.001。结论:血清cTnT浓度可能是兔多柔比星心脏毒性较早期诊断指标。

OBJECTIVE： To assess whether serum cTnT level could be a useful marker for the early detection of anthracycline-induced cardiotoxicity.METHODS： Forty-four male rabbits were entered into the study.Eight rabbits were randomly selected to form control group（saline control）.The remaining rabbits were randomly selected to create groups 1-4.Group 1 through 4 received intravenous injections of 2 mg/kg doxorubicin at weekly intervals of 1 week（8 rabbits,group 1）,2 weeks（8 rabbits,group 2）,4 weeks（9 rabbits,group 3）,or 8 weeks（11 rabbits,group 4）.Echocardiography was performed to measure left ventricular ejection fraction（LVEF）,shortening fraction（FS）,and E/A ratio.Serum cTnT concentrations were quantified by a rabbit-specific enzyme-linked immunosorbant assay（ELISA）.Cardiotoxicity scores were assessed by light microscopy using the method of Billingham and also by electron microscopy.RESULTS： Decreased LVEF,FS and E/A were detected in group 4（P0.05）.Compared with control group,cTnT levels significantly increased in group 3（P0.05）.The rabbits in group 4 had higher cTnT levels than those in the other groups（P0.05）.Myocardial lesions were significantly more severe in group 3 than that in control group（P0.05）.Myocardial lesions were significantly the most severe in group 4（P0.05）.Mitochondria swell or disruption was demonstrable by electron microscopy in the rabbits receiving two-week doxorubicin or more.The extent of myocardial injury was proportional to doxorubicin dose.There was a positive correlation between cTnT levels and cardiomyopathy scores（r=0.887,P0.001） and cumulative dose of doxorubicin（r=0.916,P0.001）.CONCLUSION： Serum cTnT concentration appears to provide a sensititive method for assessing early cardiotoxicity of doxorubicin in rabbits.