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PBDE-47对INS-1细胞氧化应激和凋亡影响

Effects and mechanism of PBDE-47 on INS-1 cells

  • 摘要: 目的 探讨2,2',4,4'-四溴联苯醚(PBDE-47)对大鼠胰岛细胞瘤细胞INS-1毒性作用及机制。方法设3个PBDE-47剂量组(1、3、6 μmol/L)和二甲基亚砜溶剂对照组,染毒INS-1细胞24 h后,检测细胞存活率、凋亡率、活性氧(ROS)水平、丙二醛(MDA)含量、Fas和cytochrome C等凋亡相关基因表达水平。结果 与对照组比较,3、6 μmol/L PBDE-47组细胞存活率(77.1±5.9)%和(27.5±10.6)%均下降(P<0.05);3、6 μmol/L PBDE-47组ROS水平分别为(154.1±13.3)和(220.1±1.1),MDA含量分别为(26.1±1.0)和(32.7±2.5)μmol/L,6 μmol/L PBDE-47组细胞凋亡率为(38.4±4.2)%,与对照组比较均有增加(P<0.05);与对照组比较,高剂量PBDE-47组Fas及cytochrome C基因表达水平均有增加(P<0.05)。结论 PBDE-47可诱导INS-1细胞凋亡,氧化应激和线粒体信号通路可能参与PBDE-47对INS-1细胞的毒性作用。

     

    Abstract: Objective To study the toxic effects and mechanism of 2,2',4,4'-tetrabromodiphenyl ethers(PBDE-47) on INS-1 cells.Methods INS-1 cells were exposed to PBDE-47 at concentrations of 1,3,and 6 μmol/L in vitro and dimethyl sulfoxide(DMSO) was used as solvent control.After 24 hours,the rate of cellular survival,percentage of apoptosis,intracellular reactive oxygen species(ROS) level,malondialdehyde(MDA) content,and expression levels of cytochrome C and Fas genes were determined.Results Compared with the control group,both the rate of cellular survival in 3 μmol/L PBDE-47 treatment group (77.1±5.9%) and 6 μmol/L PBDE-47 treatment group(27.5±10.6%) were decreased significantly(P<0.05).The ROS levels in 3 μmol/L and 6 μmol/L PBDE-47 treatment groups were 154.1±13.3 and 220.1±1.1;MDA content in 3 μmol/L and 6 μmol/L PBDE-47 treatment groups were 26.1±1.0 μmol/L and 32.7±2.5 μmol/L,respectively,and the percentage of apoptosis in 6 μmol/L PBDE-47 treatment group was 38.4±4.2%,all of them were higher than those in the control group(P<0.05 for all).The expression levels of the cytochrome C and Fas genes were significantly increased with the increment of PBDE-47 concentration(P<0.05).Conclusion PBDE-47 may induce apoptosis of INS-1 cells and oxidized stress and the mitochondria signal passage may play an important role in the apoptosis induced by PBDE-47.

     

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