三维（3D）重组皮肤模型已证实在模拟体内代谢条件、给药浓度及反应靶器官毒性特点方面具有突出优势。近年来已有多家公司构建3D重组人工皮肤模型，且一些制药公司已将3D细胞模型应用于药物的早期毒性筛选。我国动物实验替代方法的研究仍处于起步阶段，利用3D重组皮肤模型进行体外安全性评价成为目前替代方法的研究热点之一。综述人3D重组皮肤模型在遗传毒性评价中体外微核试验和彗星试验的研究进展，并对该模型在外用药物体外替代遗传毒性评价中的应用前景进行探讨。

The three-dimensional (3D) reconstructed human skin model has been proved to have promising advantages in simulating the metabolic conditions in vivo, the concentration of administration and the toxicity characteristics on the targeted organs. In recent years, the 3D reconstructed skin models have been developed by many companies, and some pharmaceutical companies have launched research on the application of 3D cell model in the early toxicity screening of drugs. However, the research on alternative methods of animal test in China is still in its infancy, and in vitro safety evaluation using 3D reconstructed epidermis has become one of the research hotspots. In this article, the research progress of 3D reconstructed human epidermis in vitro micronucleus test and comet assay in genotoxicity evaluation was reviewed, and its application prospect in in vitro alternative genotoxicity evaluation of drugs was discussed.

R965.1

国家自然科学基金资助项目（81503347，81503068）；国家“十三五”重大新药创制专项（2018ZX09201017）