T-2毒素对小鼠胚胎干细胞的氧化损伤作用

T-2 toxin induces oxidative damage in the differentiated murine embryonic stem cells

目的应用小鼠胚胎干细胞(mESC)作为模型探讨T-2毒素对mESC的作用靶点与作用机制。方法选用0.5 ng/ml T-2毒素处理分化过程中的mESC 24、72和120 h,流式细胞术检测mESC的活性氧簇(ROS)的生成,比色法检测mESC的抗氧化防御酶活性,包括超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GPx)的活力变化,以及脂质过氧化产物丙二醛(MDA)的含量。结果 0.5 ng/ml T-2毒素作用72与120 h,mESC中ROS大量蓄积,抗氧化防御酶(SOD、GPx)活力下降,MDA增加,其效应呈现时间依赖关系。自由基清除剂(Trolox,200μmol/L)预处理可以降低T-2毒素对mESC抗氧化防御酶活力的抑制作用,减轻T-2毒素引起的mESC中ROS的蓄积以及MDA的增加。结论低剂量T-2毒素染毒引起mESC的氧化损伤是其发育毒性的重要机制之一。

Objective T-2 toxin’s embryonic toxicity mechanism and targets were investigated in this study by using differentiated murine embryonic stem cells（ mESC） model.Methods At the time of differentiation 24,72 and 120 h,differentiated ESCs were explored to 0.5 ng /ml T-2 toxin.The indexes of oxidative stress,including cellular reactive oxygen species（ ROS） and the enzyme activity of superoxide dismutase（ SOD） and glutathione peroxidase（ GPx）,and lipid peroxidation product malondialdehyde（ MDA） content were detected at the time of differentiation 24 h.Results After 0.5 ng /ml T-2 toxin exposure 72 and 120 h,the significant decrease of SOD and GPx activity,and the increase of ROS and MDA were observed.However,T-2 toxin-induced oxidative stress and inhibition of antioxidant enzymes（ SOD,GPx） activity in differentiated ES cells recovered signicantly in the presence of the antioxidant Trolox.Conclusion Taken together,these results demonstrate that oxidative damage induced by low-dose T-2 toxin long term exposure plays an important role in T-2toxin embryonic toxicity mechanism.