基于组学技术的心脏毒性评价新方法及在中药安全性研究中的应用

本项目拟以全能的小鼠胚胎干细胞（mESC）为主要研究对象，基于基因组学和代谢组学的研究策略，开展mESC组学技术的药物心脏毒性评价的可行性研究，并应用到中药毒性评价中。首先建立稳定、可控的mESC和胚胎干细胞诱导的心肌细胞（mESCs-CM）的培养方法，采用组学技术筛选具有心脏毒性药物作用于mESC、mESCs-CM和小鼠的差异基因和代谢标志物。整合mESC、mESC-CM和小鼠的组学数据，寻找其差异和相关性，明确mESC组学技术的心脏毒性标志物，阐述其所涉及的代谢途径和生物学意义。进而将mESC整合生物标志物应用到中药心脏毒性评价中，采用模式识别技术判断该方法的准确性，为建立基于mESC组学技术的药物心脏毒性体外评价方法提供实验依据。

Based on genomics and metabolomics, we carry out a feasibility study on the use of the mouse embryonic stem cells (mESC) to evaluate the cardiotoxicity of Traditional Chinese Medicines. Firstly, we establish stable and controllable methods to culture mESC and mESC-CM, then using omics technology find the changes in their genes and metabolites caused by cardiotoxic agent. By using statistical tools, we integrate the omics data from mESC, mESC-CM and mouse to confirm markers for cardiac toxicity in mESC and elaborate their involvement in metabolic pathways and their biological significance. Finally, using these markers to evaluate Traditional Chinese Medicines safety, then apply pattern recognition technology to validate the accuracy of this method. The aim of this study is to provide an experimental basis for the in vitro evaluation method of drugs' cardiotoxicity based on mESC omics technology.