摘要:
研究了玉米赤霉烯酮(Zearalenone,ZEA)及黄曲霉毒素B1(Aflatoxin B1,AFB1)单独及联合作用人肝癌HepG2细胞后,多参数细胞生物学指标的变化及凋亡相关靶点基因的表达,并使用效应相加模型对联合毒性方式进行评价。结果显示,ZEA及AFB1均呈时间、剂量依赖性地抑制HepG2细胞活力,其24 h的IC50分别为78.57和18.04 μmol/L。与单独组相比,联合组显著(P<0.05)降低细胞活力并增加死亡率,提高细胞膜通透性、钙离子浓度、胞内活性氧(ROS)水平及DNA损伤程度。qRT-PCR结果显示ZEA及AFB1可通过显著(P<0.05)提高p53、Caspase-3、Bax的mRNA表达水平,同时显著(P<0.05)降低Bcl-2的表达来诱导HepG2细胞凋亡。对ZEA和AFB1的联合毒性作用方式进行评价,表现为协同作用。
Abstract:
The current study was to investigate the joint toxicity of zearalenone(ZEA)and aflatoxin B1(AFB1)on HepG2 cells. Changes in multi-parameter cell biology indicators and expression of apoptosis-related target genes were performed,and the combined toxicity model was used to evaluate the combined toxicity pattern. The results demonstrated that,ZEA and AFB1 had dose- and time-dependently decreased with the viability of HepG2 cells,and the IC50 values was 78.57 and 18.04 μmol/L at 24 h respectively. Compared with the individual group,the combined group could significantly(P<0.05)reduced cell viability and increased cell death rate,membrane permeability,intracellular calcium level,reactive oxygen species(ROS),and DNA damage. The results of qRT-PCR showed that,ZEA and AFB1 could induce apoptosis in HepG2 cells by significantly(P<0.05)increasing the mRNA expression levels of p53,Caspase-3 and Bax,and significantly(P<0.05)decreasing the expression of Bcl-2.The combined toxicity modes of ZEA and AFB1 were evaluated according to the additive effect model,which showed synergistic effect.
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