心肌毒性是抗抑郁药研发过程中早期毒性评价的重要指标之一。寻找能够快速、准确、敏感反映抗抑郁药物对人心肌毒性作用的体外替代模型和方法是抗抑郁药物研发面临的重要挑战和瓶颈问题。由于种属差异，动物实验并不能完全预测人体对药物的实际反映，且操作繁琐、成本高，不被作为早期评价的首选方式；传统孔板培养为静态培养方式，无法精确模拟药物在不同组织器官的代谢过程及毒性作用。因此，本项目拟以极具发展潜力的器官芯片为核心技术，构建人源性心肌、肝细胞动态共培养体系，以抗抑郁药氯丙咪嗪为模型药物，考察药物经肝代谢后对心肌细胞的毒性作用，并进一步阐明氯丙咪嗪的心肌毒理效应及可能的机制，建立一种集药物代谢和毒性评价为一体的新体系、新方法，以期为新药研发的早期心脏毒性评价提供全新的思路和技术平台。

Cardiotoxicity is one of bottlenecks in the development of antidepressants. It is imperative to develop a suitable alternative models with rapid, effective and sensitive features for testing cardiotoxicity in vitro. The animal experiments fail to predict the real processes of the drugs in human body. In addition, existing cell-based model failed to accurately mimic the metabolic process and toxicity in different organs in vivo due to the applications of single cells in a dish. In this project, we will develop a novel microfluidic model that mimics the process of metabolism and toxicity of clomipramine in human body by using human hepatocytes and cardiomyocytes in the way of co-culture microsystem. In addition, we further investigate the mechanism of cardiotoxicity of clomipramine in this model. This project will provide a powerful platform and alternative model for early toxic screening of new drug and drug safety evaluation.