目的 建立高通量的高内涵分析（HCA）技术，探讨何首乌致肝损伤的可能物质及作用机制。方法 人源肝癌细胞HepG2分别经不同质量浓度的何首乌不同极性提取物、何首乌主要单体成分二苯乙烯苷、芦荟大黄素、大黄素甲醚、儿茶素、大黄酚、大黄素、大黄酸、没食子酸孵育24 h后，利用Hoechst 33342等荧光探针对细胞进行染色，利用HCA技术检测并分析药物在不同浓度或不同孵育时间时对HepG2的细胞数目、细胞核形态、线粒体质量和线粒体膜电位的影响。结果 何首乌醋酸乙酯提取物和二氯甲烷提取物在1 000 μg/mL时对HepG2细胞增殖、形态和线粒体质量均有显著的影响，醋酸乙酯提取物还引起线粒体膜电位的明显下降。何首乌各单体成分在较低浓度（0.01、1 μmol/L）时对细胞无显著影响；而在较高浓度（100 μmol/L）时，芦荟大黄素、大黄素、大黄酸和没食子酸可引起细胞数目的明显下降，芦荟大黄素还引起细胞核的肿胀、导致细胞核面积增大。由大黄素和大黄酸的量效曲线可知，二者对细胞各指标的半数毒性浓度（TC₅₀）值与文献报道基本一致。各成分不同孵育时间（24、48、72 h）对细胞数目和细胞核面积的影响未出现显著差异。结论 蒽醌类成分芦荟大黄素、大黄素、大黄酸和没食子酸可能是何首乌致肝毒性的主要成分，由各单体对线粒体质量和线粒体膜电位的影响推测何首乌致肝毒性可能与线粒体介导的细胞凋亡有关。HCA技术适用于中药复杂体系的肝毒性评价。

Objective A high-content analysis (HCA) method was established for the in vitro evaluation of traditional Chinese medicine and the potential hepatotoxicity components and mechanism of Polygonum multijiorum were discussed. Methods HepG2 cells were incubated with different concentration and different incubation time of P. multijiorum extracts and components and then cells were stained with three fluorescent probes, then HCA was applied to detect the cell number, nucleus area, mitochondrial mass, and mitochondrial membrane potential. Results The ethyl acetate extract and dichloromethane extract had served hepatotoxicity. No significant changes were observed at low concentration (0.01 and 1 μmol/L) of P. multijiorum components; However, the cell number of aloe emodin, emodin, rhein, and gallic acid decreased significantly at the concentration of 0.1 μmol/L. Aloe emodin also caused the nuclear swollen. The TC₅₀ values of emodin and rhein obtained from the dose-response curves were similar to the previous reports. Conclusion The aloe emodin, emodin, rhein, and gallic acid have potential hepatotoxicity that P. multijiorum induces liver injury. The hepatotoxicity of P. multijiorum may be related to mitochondria-mediated apoptosis according to the influence of P.multijiorum components on mitichondrial mass and mitochondrial membrane potential from the results. The HCA is applicable to evaluate the hepatotoxicity of traditional Chinese medicine.

重大新药创制（2015ZX09501004）；国家自然科学基金资助项目（81473543）