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目的 研究邻苯二甲酸二(2-乙基己)酯(DEHP)在体内的代谢物邻苯二甲酸单二乙基酯(MEHP)对小鼠正常肝细胞AML12和人肝癌细胞HepG2的毒性效应，并初步探讨其作用机制。方法 体外培养AML12，分成对照组和MEHP模型组，MEHP模型组分为200、400、800μmol/L三种不同浓度。通过RT-qPCR、Western blot等方法检测细胞形态、细胞活力、凋亡、活性氧(ROS)、超氧化物歧化酶(SOD)以及与凋亡有关的因子mRNA表达水平，观察细胞形态。结果 随着MEHP的浓度增加，细胞活性明显出现抑制，半数抑制浓度(IC50)约为393μmol/L；与对照组相比，模型组的ROS水平明显增加(P<0.001)，且SOD活性有所下降，MDA表达显著性上升(P<0.001)；与对照组相比，抑制凋亡因子bcl-2表达水平降低，促凋亡相关因子(bax、caspase3等)表达增加(P<0.001)，且相关炎症因子(IL-1、IL-6、TNF-α)表达水平显著上升。结论 MEHP诱导肝脏细胞损伤与细胞凋亡、氧化应激相关，这对研究MEHP致肝损伤的机制具有重要意义。
Abstract：Objective To investigate the toxic effects of monoethylhexyl phthalate(MEHP), a metabolite of di(2-ethylhexyl) phthalate(DEHP), on normal hepatocytes AML12 and human hepatocellular carcinoma cells HepG2, and preliminarily explore its mechanisms.Methods AML12 cells were cultured in vitro and divided into a control group and a MEHP model group, with the MEHP model group further subdivided into three concentrations(200, 400, and 800 μmol/L). The expression levels of cell morphology, cell viability, apoptosis, reactive oxygen species(ROS), superoxide dismutase(SOD), and mRNA of apoptosis-related factors were detected using methods such as RT-qPCR and Western blot, with cellular morphology observed accordingly.Results As MEHP concentration increased, cell viability was significantly inhibited, with a half maximal inhibitory concentration(IC50) of approximately 393 μmol/L. Compared to the control group, the model group exhibited significantly elevated ROS levels(P<0. 001), reduced SOD activity, and a marked increase in MDA expression(P<0. 001). Additionally, the expression of the anti-apoptotic factor bcl-2 decreased, while pro-apoptotic factors(bax, caspase3, etc.) increased(P<0. 001), along with significantly elevated levels of inflammatory factors(IL-1, IL-6, TNF-α).Conclusion MEHP-induced liver cell damage is associated with apoptosis and oxidative stress, which have important implications for studying the mechanisms of MEHP-mediated liver injury.
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基本信息:
DOI：10.19405/j.cnki.issn1000-1492.2026.08.008
中图分类号:R99
引用信息:
[1]王浩泽,柏楠,俞军,等.MEHP对小鼠肝细胞AML12和人肝癌细胞HepG2的细胞毒性效应研究[J].安徽医科大学学报,2026,61(08):1392-1399.DOI:10.19405/j.cnki.issn1000-1492.2026.08.008.
基金信息:
国家自然科学基金项目（编号：82073566）~~
2026-07-20
2026-07-20
2026-07-20