[关键词]
[摘要]
玉米赤霉烯酮毒素(ZEA)是一种非甾体霉菌毒素,存在于霉变的谷物中,具有类其雌激素样作用,能引起生殖机能异常。但是关于ZEA的肾脏毒性研究的比较少。白藜芦醇(RSV)是在红酒、葡萄中存在的一种多酚化合物,具有抗氧化作用。通过不同浓度梯度的ZEA(3、15、75、150、300 μM)、RSV(0、0.01、0.1、1、10、100 μM)和DL-α-lipoic acid(LA)(0、1、10、100、1000 μM)作用于人胚肾HEK293细胞24 h,细胞活性的测定显示ZEA对HEK293细胞的IC50为80 μM,而RSV(<10 μM)和LA对细胞无明显损伤。利用RSV和LA对细胞进行预处理24 h之后,再将ZEA作用于细胞24 h,通过细胞增殖力、ROS、MDA、SOD、MnSOD指标的检测,表明RSV/LA能提高细胞的抗氧化性,减轻ZEA产生的细胞毒性和氧化损伤。同时,ZEA可引起促凋亡基因Bax的显著表达,但对于SIRT1和抗凋亡基因Bcl-2的表达没有影响,而RSV预处理能显著提升SIRT1和Bcl-2的表达,降低Bax的表达,发挥抗凋亡作用。
[Key word]
[Abstract]
Zearalenone (ZEA), a non-steroidal estrogenic mycotoxin that is widely present in moldy grains, has estrogen-like activity and can cause reproductive dysfunction. However, there have been few studies on the nephrotoxicity of ZEA. Resveratrol (RSV) is a polyphenolic compound present in red wine and grapes that possesses antioxidant activity. Human embryonic kidney (HEK 293) cells were treated with different concentrations of ZEA (3, 15, 75, 150, and 300 ?M), RSV (0, 0.01, 0.1, 1, 10, and 100 ?M), and DL-?-lipoic acid (LA) (0, 1, 10, 100, and 1000 ?M) for 24 h. Cell viability measurements showed that the half maximal inhibitory concentration (IC50) of ZEA against HEK293 cells was 80 ?M, while RSV and LA treatment did result in significant damage to the cells. Cells were pretreated with RSV and LA for 24 h, followed by ZEA treatment for 24 h. The cell proliferative ability and levels of reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), and manganese form of SOD (MnSOD) were measured, and the results indicated that RSV/LA could enhance the cellular antioxidant activity and reduce the cytotoxicity and oxidative damage caused by ZEA. Additionally, ZEA treatment increased expression of the pro-apoptotic gene Bax, but had no impact on the expression of SIRT1 or the anti-apoptotic gene Bcl-2. In contrast, RSV pretreatment significantly increased the expression of both Bcl-2 and SIRT1, reduced the expression of Bax, and had an anti-apoptotic effect.
[中图分类号]
[基金项目]
国家农业部公益项目(201203069)