血清GPBB早期诊断蒽环类药物的心脏毒性

Serum GPBB as a Marker for Early Detection for Anthracycline-induced Cardiotoxicity in Rabbits

【目的】研究血清GPBB浓度是否可以成为蒽环类药物的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;实验组新西兰兔每次静脉注射阿霉素2mg/kg,每周1次,根据实验周数不同,实验组分为4组,分别为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峰比率。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阿霉素心脏毒性。【结果】8周组新西兰兔LVEF、FS和E/A比率均下降(P<0.05)。4周组新西兰兔血清GPBB浓度明显高于对照组血清GPBB浓度[(30±8)ng/mLvs(21±8)ng/mL,P<0.05];8周组新西兰兔GPBB浓度为(38±3)ng/mL,显著高于其余各组新西兰兔血清GPBB浓度(P<0.05)。光镜下4周组新西兰兔心肌损害比对照组、1周组和2周组新西兰兔心肌损害严重(P<0.05);8周组新西兰兔心肌损害最严重(P<0.05)。电镜下线粒体水肿或断裂可见于2周组、4周组和8周组新西兰兔。血清GPBB浓度与阿霉素累积剂量(r=0.442,P<0.001)和心肌损害程度(r=0.467,P<0.001)均呈正相关。【结论】血清GPBB浓度可能是兔阿霉素心脏毒性较早期诊断指标。

[Objective] This study was to assess whether serum GPBB 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 animals were randomly selected to create groups 1-4.Thus,group 1 through 4 received intravenous injections of 2 mg/kg doxorubicin at weekly intervals of 1 week（group 1,8 rabbits）,2 weeks（group 2,8 rabbits）,4 weeks（group 3,9 rabbits）,or 8 weeks（group 4,11 rabbits）.Echocardiography was performed to measure left ventricular ejection fraction（LVEF）,shortening fraction（FS）,and E/A ratio.Serum GPBB 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 ratios were detected in group 4（P 0.05）.Compared with control group,serum GPBB levels significantly increased in group 3（30 ± 8 ng/mL vs 21 ± 8 ng/mL,P 0.05）.Serum GPBB levels in group 4 were 38 ± 3 ng/mL,which were higher than those in the other groups（P 0.05）.Myocardial lesions in group 3 were significantly more severe than those in control group,group 1 and group 2（P 0.05）.Myocardial lesions were the most severe in group 4（P 0.05）.Mitochondria swell or disruption was demonstrable by electron microscopy in group2,group3,and group 4.There was a positive correlation between serum GPBB levels and the doses of doxorubicin（r = 0.442,P 0.001） and cardiomyopathy scores（r = 0.467,P 0.001）.[Conclusions] Serum GPBB concentrations appear to provide a sensitive method for assessing early cardiotoxicity of doxorubicin in rabbits.