十溴联苯醚诱导小鼠海马神经元细胞氧化应激和凋亡的机制  

The mechanisms of hippocampal neurons exposed to PBDE-209 induce oxidative stress and apoptosis

作　　者：林浩飞 戴瑞雪[1] 李俊[1] 李玉荣[1] 唐静[1] 翟金霞[1] 

机构地区：[1]安徽医科大学公共卫生学院劳动卫生与环境卫生学系,合肥230032

出　　处：《卫生研究》2016年第6期977-983,共7页Journal of Hygiene Research

基　　金：安徽省自然科学基金(No.1408085MH192);安徽医科大学博士基金(No.XJ201201)

摘　　要：目的探索十溴联苯醚(PBDE-209)诱导小鼠海马神经元细胞凋亡的潜在机制。方法原代海马神经元细胞和海马神经元细胞系HT-22用0、6.25、12.5、25、50和100μg/mL PBDE-209处理24 h。检测原代海马神经元细胞SOD活性,MDA、NO和GSH的含量,用Annexin V/PI双染法检测海马神经元细胞系HT-22细胞凋亡情况,用免疫蛋白印迹Western blot检测Bax、Bcl-2、CHOP、GRP78、PERK和Caspase-12蛋白表达水平。结果染毒组原代海马神经元细胞和HT-22细胞系细胞存活率显著降低(P<0.05)。原代海马神经元细胞MDA、NO含量显著升高(P<0.05),GSH含量、SOD活性显著降低(P<0.05);原代海马神经元细胞的Bax/Bcl-2比值、CHOP、Caspase-12蛋白表达水平升高(P<0.05)。HT-22细胞系GRP78、PERK、Caspase-12表达水平和细胞凋亡率升高(P<0.05)。结论氧化应激和内质网应激可能参与PBDE-209诱导的海马神经元细胞凋亡过程。Objective To determine the potential mechanisms of PBDE-209 induce apoptosis of the hippocampal neurons.Methods The primary fetal hippocampal neurons and hippocampus neurons cell line HT-22 were exposed to the concentrations of 0（ solvent control）,6.25,12.5,25,50 and 100 μg/mL PBDE-209 for 24 h.The SOD activity,MDA,NO and GSH contents in primary fetal hippocampal neurons were examined.The apoptosis of hippocampus neurons cell line HT-22 was observed using Annexin V/PI.The expressions of Bax, Bcl-2, CHOP, GRP78, PERK, Caspase-12 were measured by Western blot.Results The results showed that the difference was significant（ P 〈 0.05）of neuronal survival between the experimental groups and control groups and the difference was more obvious with the increasing dose of PBDE-209 which was observed in primary fetal hippocampal neurons and HT-22 cell lines.The increasing of Bax/Bcl-2（ P 〈 0.05）,expression of CHOP and Caspase-12 in primary fetal hippocampal neurons（ P 〈 0.05）,malondialdehyde（ MDA） content and NO content（ P 〈 0.01） were also observed.Additionally,the results also indicated that PBDE-209 deceased activity of superoxidedismutase（ SOD） and glutathione（ GSH）（ P 〈 0.05）.Meanwhile,the experiments of the HT-22 cell line showed that PBDE-209 could increase the expression of GRP78,PERK and Caspase-12 and apoptosis.Conclusion The oxidative stress and endoplasmic reticulum stress may involve in the apoptosis of nerve cells caused by PBDE-209.

关 键 词：十溴联苯醚 内质网应激 氧化应激 海马神经元 细胞凋亡 

分 类 号：R994.6[医药卫生—毒理学] Q593.2[医药卫生—药学]