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引用本文:冯红敏,胡玥,盛云华,唐黎明,陈桂良.细胞体外暴露试验在吸入毒理学研究中的应用进展[J].中国现代应用药学,2019,36(5):617-624.
FENG Hongmin,HU Yue,SHENG Yunhua,TANG Liming,CHEN Guiliang.Application Progress of in Vitro Cell Exposure Test in Inhalation Toxicology[J].Chin J Mod Appl Pharm(中国现代应用药学),2019,36(5):617-624.
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细胞体外暴露试验在吸入毒理学研究中的应用进展
冯红敏1,2,3, 胡玥1,2,3, 盛云华3, 唐黎明2,3, 陈桂良4
1.复旦大学药学院, 上海 201203;2.中国医药工业研究总院, 上海 201203;3.上海市食品药品检验所药理毒理室, 上海 201203;4.上海药品审评核查中心, 上海 201203
摘要:
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。
关键词:  吸入毒理学  呼吸道体外模型  气液界面  暴露  检测指标
DOI:10.13748/j.cnki.issn1007-7693.2019.05.022
分类号:R99
基金项目:中国烟草总公司科技重大专项[110201501002(XX-02)];云南省烟草化学重点实验室2017年度开放基金项目(KCFZ-2017-1096)
Application Progress of in Vitro Cell Exposure Test in Inhalation Toxicology
FENG Hongmin1,2,3, HU Yue1,2,3, SHENG Yunhua3, TANG Liming2,3, CHEN Guiliang4
1.School of Pharmacy, Fudan University, Shanghai 201203, China;2.China Stata Institute of Pharmaceutical Industry, Shanghai 201203, China;3.Department of Pharmacology & Toxicology, Shanghai Institute for Food and Drug Control, Shanghai 201203, China;4.Shanghai Center for Drug Evaluation and Inspection, Shanghai 201203, China
Abstract:
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.
Key words:  inhalation toxicology  in vitro model of respiratory tract  air-liquid interface  exposure  detection indexs
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