亚硒酸钠和三氧化二砷诱导人急性早幼粒细胞白血病细胞系NB4细胞凋亡机制的比较  

The Comperison between the Mechanisms of Sodium Selenite Induced Apoptosis and Arsenic Trioxide Induced Apoptosis in Human Acute Promyelocytic Leukemia Cell Line NB4 Cells

作　　者：左路[1] 李剑[1] 沈悌[1] 张之南[1] 

机构地区：[1]中国医学科学院,中国协和医科大学,北京协和医院血液科,北京100730

出　　处：《中国实验血液学杂志》2002年第3期195-200,共6页Journal of Experimental Hematology

摘　　要：为比较亚硒酸钠 (Na2 SeO3 )和三氧化二砷 (As2 O3 )诱导NB4细胞凋亡的作用机制 ,本研究应用MTT实验、DNA琼脂糖电泳、细胞内DNA含量检测研究细胞生长抑制和细胞凋亡 ,用化学发光法、化学比色法检测细胞内活性氧和还原型谷胱甘肽 ,用流式细胞术检测细胞内线粒体膜电位。结果显示 :5 μmol/L亚硒酸钠和 1μmol/L三氧化二砷作用 2 4小时后均能诱导NB4细胞凋亡。在诱导细胞凋亡的过程中 ,亚硒酸钠和三氧化二砷组均伴有细胞内活性氧水平的提高和线粒体膜电位下降 ,但在亚硒酸钠组还伴有细胞内还原型谷胱甘肽下降。用N乙酰半胱氨酸提高细胞内还原型谷胱甘肽后 ,增强了硒诱导NB4细胞凋亡和氧化应激的作用 ,但是抑制了砷诱导细胞凋亡和氧化应激的作用。结论 :亚硒酸钠和三氧化二砷同样可以诱导NB4细胞的凋亡 。In order to explore the differences between the mechanisms of selenite induced apoptosis and arsenic induced apoptosis in NB4 cells, growth inhibition was determined by MTT test, apoptosis determined by DNA electrophoresis and analysis of intracellular DNA contents, reactive oxygen species and reduced glutathione in the cell were measured by Lucigenin dependent chemoluminescent (CL) test and spectrophotometry, and mitochondrial transmembrane potential was measured by flow cytometry. The results showed that: 5 μmol/L sodium selenite similar to 1 μmol/L arsenic trioxide could induce the apoptosis of NB4 cells after treatment for 24 hours. Both could elevate the level of reactive oxygen species and intensify mitochondrial transmembrane potential collapse, accompanied with decrease of reduced glutathione centent. The effect of selenium selenite on these aspects was more siginificant than those of arsenic trioxide. Elevation of intracellular glutathione in N acytlcysteine pretreated NB4 cells could enhance the selenite induced apoptosis and oxidative stress,but ameliorate the arsenic trioxide induced apoptosis and oxidative stress. It was concluded that sodium selenite and arsenic trioxide can induce the apoptosis of NB4 cells, but there are significant differences between the mechanisms of selenite induced and arsenic induced apoptosis in NB4 cells, praticularly in the influence of intracellular glutathione content on the drug action.

关 键 词：亚硒酸钠 三氧化二砷 急性早幼粒细胞白血病 细胞凋亡 NB4细胞 药理学 APL 流细胞术 急性早幼粒细胞白血病细胞 

分 类 号：R733.71[医药卫生—肿瘤] R965[医药卫生—临床医学]