Evaluation of doxorubicin toxicity on cardiomyocytes using a dual functional extracellular biochip
Evaluation of doxorubicin toxicity on cardiomyocytes using a dual functional extracellular biochip
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使用双功能细胞外生物芯片评估阿霉素对心肌细胞的毒性。
DOI：
10.1016/j.bios.2010.07.093
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发表时间：
2010-12-15
影响因子：
12.6
通讯作者：
Wang, Ping
中科院分区：
文献类型：
--
作者：
Xiao, Lidan;Hu, Zhaoyin;Wang, Ping
目前，临床药物引起的心脏毒性发生率较高，在临床治疗前进行有效可靠的药物评价已引起人们的高度重视。阿霉素作为一种蒽环类肿瘤化疗药物，由于其对心脏的毒性，在临床应用中受到限制。本研究设计了一种集成微电极阵列和交叉指电极的双功能生物芯片ExCell，用于研究阿霉素作用下心肌细胞的电生理功能和物理状态。测定细胞外场电位和细胞-底物阻抗，分别在同一培养中同时表达这两种功能。ExCell检测结果显示了阿霉素引起的心脏毒性。阿霉素浓度为20 μ M、100 μ M和200 μ M，处理50 min后细胞外场电位幅值分别下降到93%、82%和50%。心率下降、搏动变化和Ca2+通量均出现严重异常。在电生理功能抑制过程中，细胞-基质阻抗持续下降，高浓度处理诱导细胞死亡。这些结果表明，ExCell生物芯片有潜力成为高通量药物评价分析的快速反应和精细工具。(C) 2010年Elsevier B.V.出版
Nowadays, cardiotoxicity induced by clinical drugs presents a high prevalence and has aroused great attention onto the effective and reliable drug evaluation before clinical treatment. Doxorubicin (Adriamycin), as a type of anthracycline chemotherapy agent for cancer treatment, was restricted in the clinical use because of its cardiotoxicity. In the present work, a dual functional biochip ExCell integrated with microelectrode arrays and interdigitated electrodes was designed to study the electrophysiological function and physical state of cardiomyocytes under the treatment of doxorubicin. Extracellular field potentials and cell-substrate impedance were measured to respectively express these two functions simultaneously in the same culture. The result detected by ExCell presented a portrait of cardiotoxicity induced by doxorubicin. The amplitude of extracellular field potentials decreased to 93%, 82% and 50% at 50 min treatment of doxorubicin with concentrations of 20 mu M, 100 mu M and 200 mu M, respectively. Successively, beating rate decrease, beat-to-beat variation and Ca2+ flux manifested severe abnormality. The cell-substrate impedance declined continuously in the depressing process of electrophysiological function and cell death was induced in high concentration treatment. All these result indicate that the biochip ExCell has the potential to be a fast-response and subtle tool for high-throughput drug evaluation assays. (C) 2010 Published by Elsevier B.V.