【摘要】 目的 采用多柔比星（doxorubicin，DOX）制备心肌损伤动物模型，评价各种检测心功能变化方法的意义。 方法 14只新西兰大白兔，DOX耳缘静脉注射，每周3 mg/kg，共10周。分别于给药前、第4周末及实验结束时测定血清肌钙蛋白Ⅰ（cTnI）和脑钠肽（BNP）水平，彩色多普勒超声心动图检测心功能变化，并观察心肌组织病理形态学改变及心肌细胞凋亡情况。 结果 使用DOX前后对比，血清cTnI和BNP浓度升高（Plt;0.05）；左室射血分数（LVEF）和左室短轴缩短率（LVFS）下降（Plt;0.05）；心肌组织病理显示心肌细胞出现不同程度的空泡变性与水肿，细胞间隙明显增宽，大量炎性细胞浸润。心肌细胞凋亡明显增加。 结论 结合心脏超声检查和血清cTnI、BNP指标检测可判断心肌损伤程度。【Abstract】 Objective To observe the changes of heart function caused by doxorubicin in rabbits. Methods A total of 14 New-Zealand white rabbits were intravenous-injected with doxorubicin with a dosage of 3 mg/kg intravenously once a week, and the accumulative dose was 30 mg/kg. Before the medication and at the 4th and 10th weekend after the medication, the serum levels of cardiac troponin I (cTnI) and brain natriuretic peptide (BNP) were measured; left ventricular ejection function (LVEF) and left ventricular fractional shortening (LVFS) were performed on the rabbits respectively. At the 10th weekend, the pathological changes of cardiac tissue and the apoptosis of myocardial cell were detected. Results The levels of cTnI and BNP significantly increased (Plt;0.05), and the LVEF and LVFS markedly decreased (Plt;0.05) after the administration of doxorubicin. Uneven vacuolar degeneration and edema of cardiocytes could be observed with a wide cell spaces and inflammatory cell infiltration in the histopathological slices. Conclusion The combined application of heart sonography with the detection of the serum levels of cTnI and BNP can evaluate the degree of myocardial damage of the rabbits models very well.
Fluoropyrimidines have been the standard care as ajuvant or palliative treatment for malignant gastrointestinal carcinoma over several decades. Their common adverse effects include gastrointestinal effects, myelosuppression, and hand-foot syndrome. Besides, fluoropyrimidines are the second cause of chemotherapy-induced cardiotoxicity and have the different manifestation and machanisms from anthracyclines. With the development of onco-cardiology, increasing concern is raised on fluoropyrimidine-induced cardiotoxicity. This review addresses the epidemiology, clinical manifestation, and proposed mechanisms; and also highlights the diagnosis, monitoring and management of fluoropyrimidine-induced cardiotoxicity.