细胞体外暴露试验在吸入毒理学研究中的应用进展

Application Progress of in Vitro Cell Exposure Test in Inhalation Toxicology

吸入毒理学主要研究气体、蒸气和气溶胶等可吸入物质进入呼吸道后对生物体产生的不良反应。当前,由于对实验动物伦理和福利的倡导,体外替代方法受到越来越多的关注。吸入毒理学的体外替代方法常用细胞体外暴露试验,其中体外模型的构建以及毒性评估至关重要。而研究可吸入物质对呼吸道的不良反应需要模拟呼吸道细胞在体内生长的微环境,然后将细胞暴露于上述物质中,因此吸入毒理学对细胞模型及体外暴露装置提出了更高的要求。目前,体外细胞模型从原代细胞、细胞系扩大为共培养及商品化模型。针对细胞体外暴露试验现已开发多种气液界面暴露系统,并且可实现的暴露时间也已经进一步延长。本文针对呼吸道体外模型及应用、气液界面培养及暴露系统、试验检测指标等方面对近年来国内外细胞体外暴露试验应用于吸入毒理学的研究进展进行综述。

Inhalation toxicology mainly studies toxic reaction of inhalable substances such as gases, vapors and aerosols to the organism after entering respiratory tract. Currently, in vitro alternative methods are attracting more and more attention due to the advocacy of ethics and welfare for laboratory animals. For in vitro alternatives in inhalation toxicology, the most commonly used method is in vitro cell exposure test, in which model construction and toxicity assessments are critical. Studying toxic effects of inhalable substances on respiratory tract requires simulating the micro-environment where respiratory epithelial cells grow in vivo, then exposing cells to substances. Therefore, inhalation toxicology puts higher demands on cell models and in vitro exposure devices. At present, in vitro cell models have expanded from primary cells, cell lines to co-culture and commercial cell models;a variety of air-liquid interface exposure systems have been developed, exposure time is further extended as well. In this paper, the progress of in vitro cell exposure test applied to inhalation toxicology is reviewed, including the application of in vitro model of respiratory tract, air-liquid interface culture, exposure systems and detection indexs.