一种检测中药成分毒性的心脏芯片构建

Construction of heart chip for evaluating toxicity of traditional Chinese medicine ingredients

中文关键词: 心脏毒性  器官芯片  中药  毒性检测

英文关键词: cardiotoxicity  organ chip  traditional Chinese medicine  toxicity evaluation

中文摘要:

      为确定中药安全性,有必要对中药中各成分的量效毒关系进行研究.心脏毒性是新药研究中需要格外注意的器官毒性,为了解决孔板试验中缺少细胞间相互作用以及微环境与体内差异大的问题,构建了一种在体外模拟心肌细胞与毛细血管相互作用的心脏芯片,并使用该芯片检测了雷公藤甲素、氯化两面针碱、莨菪碱3种中药成分的毒性.通过对比加药前后芯片和孔板里心肌细胞的搏动状态变化,以及细胞培养液中乳酸脱氢酶和肌钙蛋白的含量变化,发现3种中药化学成分有剂量依赖的心脏毒性,同时发现芯片内的心肌细胞比孔板内的对于药物的耐受性更强,显示了本芯片用于检测药物心脏毒性的潜力.

英文摘要:

      To evaluate the safety of traditional Chinese medicine (TCM), it is necessary to research on the dose effect toxicity relationships of TCM ingredients. Heart is an organ that may suffer from toxic effects and deserves attention in research in the development of new drugs. To solve the problems of lack of inter-cellular interactions and big differences between micro environment of well plates and real body, a heart chip that simulates the interaction between cardiomyocytes and capillaries in vitro is constructed to detect the toxicity of three TCM ingredients (triptolide, nitidine chloride and hyoscyamine). By comparing the changes of beating state of the cardiomyocytes on chip and well plate before and after the dosing, and the changes in the content of lactate dehydrogenase and troponin in the cell culture solution, it is found that the three chemical ingredients of TCM have dose-dependent cardiotoxicity. At the same time, it is found that the cardiomyocytes on the chip are more resistant to drugs than those on the well plate, this chip can be used to evaluate the cardiotoxicity of drugs.