海岸带环境过程实验室知识库

2,2’,4,4’-四溴联苯醚（BDE-47）是生物体中含量最高且毒性最强的PBDEs之一,有关BDE-47对肾细胞的毒性及其作用机制的研究仍有待补充。选取3个剂量组（低：10-6mol·L-1、中：10-5mol·L-1、高：10-4mol·L-1）及溶剂对照组,研究了BDE-47对人胚肾细胞（HEK293）的细胞凋亡率及活性氧（ROS）水平的影响;并从分子水平对细胞氧化损伤、凋亡相关蛋白（APE1及p53）及凋亡相关基因m RNA（p53、Bax、Caspase 3、Caspase 8）的表达量进行测定。实验结果显示：与对照组相比,中、高剂量组细胞凋亡率显著增加（P〈0.05）;ROS水平在中剂量组显著上升（P〈0.01）;随BDE-47浓度的变化,APE1蛋白表达量与细胞ROS水平存在一致性;p53、Bax、Caspase 8 m RNA表达量与BDE-47的浓度间存在剂量-效应关系。结果表明,BDE-47可诱导HEK293细胞凋亡及氧化应激,APE1可能是细胞ROS升高与细胞凋亡间重要的中介因子;BDE-47可以通过影响Caspase 8及线粒体途径中p53及Bax的表达诱导细胞凋亡。

Three BDE-47 concentration groups （low： 10-6 mol.L-1, medium： 10-5 mol.L-1, high： 10-4 mol.L-1） and one control group were chosen to investigate the toxic effects of BDE-47 on HEK293 cells, including cell apoptosis ratio and ROS level. Furthermore, the abundance of several proteins （APE1 and p53） and expression level of p53, Bax, Caspase 8 were also detected at molecular level. It was found that cell apoptosis was significantly increased in the medium and high concentration groups （P 〈 0.05） compared with the control. ROS level also increased significantly in the medium concentration group （P 〈 0.01）. With the increase of BDE-47 con- centrations, the variation trend of APE1 abundance was coincident with that of ROS level. Moreover, the mRNA expression level of apoptosis-related genes （1953, Bax and Caspase 8） was up-regulated with the increase of BDE-47 concentrations. These results showed that BDE-47 could cause several toxic effects on HEK293 cells, including induction of cell apoptosis and oxidative stress. APE1 was perhaps an important mediator of cell apoptosis and oxidative stress. BDE-47 could induce cell apoptosis by affecting the expression of Caspase 8 and p53, Bax through the mitochondria signal pathway.