AFB1和ZEN对HepG2细胞体外联合毒性效应及机制研究

doi:10.13560/j.cnki.biotech.bull.1985.2018-0588

生物技术通报 ›› 2018, Vol. 34 ›› Issue (11): 160-167.doi: 10.13560/j.cnki.biotech.bull.1985.2018-0588

AFB1和ZEN对HepG2细胞体外联合毒性效应及机制研究

任亚林, 李耘, 吴静

中国农业科学院农业质量标准与检测技术研究所,北京 100081

收稿日期:2018-06-28 出版日期:2018-11-26 发布日期:2018-11-28
作者简介:任亚林,女,硕士研究生,研究方向：农产品加工与安全;E-mail：1261452807@qq.com
基金资助:
国家食品安全重大专项（2017YFC1600704）,中国农业科学院创新团队项目

Combined Hepatotoxicity Assessment of Mycotoxins AFB1 and Zearalenone on Hepatocellular Carcinoma Cells HepG2 in vitro and Its Mechanisms

REN Ya-lin, LI Yun, WU Jing

Institute of Quality Standard and Testing Technology for Agro-products,Chinese Academy of Agricultural Sciences,Beijing 100081

Received:2018-06-28 Published:2018-11-26 Online:2018-11-28

摘要/Abstract

摘要： 基于HepG2肝癌细胞,从关键凋亡基因、早期损伤指标及细胞凋亡等方面研究黄曲霉毒素B1（Aflatoxin B1,AFB1）和玉米赤霉烯酮（Zearalenone,ZEN）联合肝毒性效应并探究其可能的作用机制。结果显示,1-10 μg/mL的AFB1和ZEN复合作用于细胞主要表现为协同联合效应,同时随着浓度升高,由弱拮抗效应逐步转变为增毒效应直至强协同效应;早期凋亡指针ROS随暴露时间延长升高,而GSH和MMP水平则呈现逐步下降趋势,同时0-3 h变化最为显著;随时间延长,Bax/Caspase-3表达量的比值升高,CYP1A2、CYP3A4和CYP2A6总体趋势均下调,但随时间延长该趋势更为显著;AFB1和ZEN诱导细胞联合肝毒性通过Bax,Caspase-3以及CYP450等基因互动调控实现。

关键词: 黄曲霉毒素B1, 玉米赤霉烯酮, 高内涵筛选, 肝联合毒性效应, CI模型

Abstract: Based on key apoptotic genes,early apoptosis signal indexes and apoptosis,this study used hepatocellular carcinoma Cells HepG2 cells to estimate combined hepatotoxic effects of aflatoxin B1（AFB1）and zearalenone（ZEN）and to explore its feasible mechanisms. The results showed that the combined effects of 1-10 μg/mL mycotoxins AFB1 and ZEN on the cells was synergetic,and the effect presented as weak antagonistic to toxic and further to strong synergetic with the increase of concentration. The early apoptosis indicator ROS rose with the exposure time prolonging;while GSH and MMP gradually was decreasing,and the change was the most significantly at 0 - 3 h. The ratio of Bax/Caspase-3 expression increased with the prolonging of the time;while the expressions of CYP1A2,CYP1A4 and CYP1A6 tended to be down,which was more obvious with the increase of the time. AFB1 and ZEN induced the combined hepatotoxicity via the interaction and regulation of gene Bax,Caspases-3,and CY450.

Key words: aflatoxin B1, zearalenone, high content screening, combined hepatotoxicity, combination index（CI）-isobologram equation

任亚林, 李耘, 吴静. AFB1和ZEN对HepG2细胞体外联合毒性效应及机制研究[J]. 生物技术通报, 2018, 34(11): 160-167.

REN Ya-lin, LI Yun, WU Jing. Combined Hepatotoxicity Assessment of Mycotoxins AFB1 and Zearalenone on Hepatocellular Carcinoma Cells HepG2 in vitro and Its Mechanisms[J]. Biotechnology Bulletin, 2018, 34(11): 160-167.

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AFB1和ZEN对HepG2细胞体外联合毒性效应及机制研究

Combined Hepatotoxicity Assessment of Mycotoxins AFB1 and Zearalenone on Hepatocellular Carcinoma Cells HepG2 in vitro and Its Mechanisms

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