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心脏脂肪酸结合蛋白可能不是兔蒽环类药物诱导性心脏毒性的早期生物标志物。

Heart fatty acid-binding protein may not be an early biomarker for anthracycline-induced cardiotoxicity in rabbits.

机构信息

State Key Laboratory of Oncology in South China, 510060 Guangzhou, Guangdong, People's Republic of China.

出版信息

Med Oncol. 2012 Sep;29(3):2303-8. doi: 10.1007/s12032-011-9843-x. Epub 2011 Feb 10.

Abstract

The objective of this study was to investigate the feasibility of using serum heart fatty acid-binding protein (H-FABP) concentrations as an early biomarker for doxorubicin-induced myocardial damage. Forty-four male rabbits were randomly divided into a control (8 rabbits) or one of four doxorubicin groups (8 rabbits in each group). Rabbits in the control group received saline, whereas rabbits in the doxorubicin group received 2 mg/kg doxorubicin weekly for 1-8 weeks. Rabbits in the doxorubicin groups received doxorubicin 2 mg/kg for one (Group 1, 8 rabbits), two (Group 2, 8 rabbits), four (Group 3, 9 rabbits), or eight (Group 4, 11 rabbits) weeks. Echocardiography was performed to measure left ventricular ejection fraction (LVEF), shortening fraction (FS), and E/A ratio. Cardiotoxicity scores were assessed by light microscopy using Billingham's method and also by electron microscopy. Serum H-FABP concentrations were quantified by a rabbit-specific enzyme-linked immunosorbent assay. Decreased LVEF, FS, and E/A ratio were detected in Group 4 (P < 0.05). Billingham cardiomyopathy scores of the rabbits in Group 3 were significantly higher (P < 0.05) than those of rabbits in the control group or Groups 1 or 2. Billingham cardiomyopathy scores in Group 4 were the highest of all groups (P < 0.05). Myocardial injury was demonstrable by electron microscopy in rabbits in Groups 2, 3, and 4. Compared with the control group, serum H-FABP concentrations increased only in Group 4 (P < 0.05). Serum H-FABP concentrations may not be a sensitive method for assessing early cardiotoxicity of doxorubicin.

摘要

本研究旨在探讨血清心脏型脂肪酸结合蛋白(H-FABP)浓度作为蒽环类药物诱导心肌损伤早期生物标志物的可行性。44 只雄性家兔随机分为对照组(8 只)或蒽环霉素组(每组 8 只)。对照组给予生理盐水,蒽环霉素组每周给予 2mg/kg 蒽环霉素,共 1-8 周。蒽环霉素组中,有 8 只家兔给予 2mg/kg 蒽环霉素 1 周(第 1 组),8 只家兔给予 2mg/kg 蒽环霉素 2 周(第 2 组),9 只家兔给予 2mg/kg 蒽环霉素 4 周(第 3 组),11 只家兔给予 2mg/kg 蒽环霉素 8 周(第 4 组)。通过超声心动图测量左心室射血分数(LVEF)、缩短分数(FS)和 E/A 比值。采用 Billingham 法通过光镜和电镜评估心脏毒性评分。通过兔特异性酶联免疫吸附试验定量检测血清 H-FABP 浓度。第 4 组的 LVEF、FS 和 E/A 比值降低(P<0.05)。第 3 组的 Billingham 心肌病评分明显高于对照组或第 1 组或第 2 组(P<0.05)。第 4 组的 Billingham 心肌病评分最高(P<0.05)。第 2 组、第 3 组和第 4 组的家兔通过电镜可观察到心肌损伤。与对照组相比,仅第 4 组的血清 H-FABP 浓度升高(P<0.05)。血清 H-FABP 浓度可能不是评估蒽环类药物早期心脏毒性的敏感方法。

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