2,2’,4,4’-四溴联苯醚对原代新生大鼠海马细胞氧化应激、DNA损伤和凋亡的影响  

Effects of PBDE-47 on Oxidative Stress,DNA Damage,and Apoptosis in Primary Rat Hippocampal Neurons

作　　者：何卫红[1] 何平[1] 张明[1] 夏涛[1] 陈学敏[1] 王爱国[1] 

机构地区：[1]华中科技大学同济医学院公共卫生学院劳动卫生与环境卫生系环境与健康教育部重点实验室,湖北武汉430030

出　　处：《环境与健康杂志》2007年第1期19-22,共4页Journal of Environment and Health

基　　金：国家自然科学基金资助项目(45090393)

摘　　要：目的探讨2,2’,4,4’-四溴联苯醚(2,2’,4,4’-tetrabromodiphenylethers,PBDE-47)对原代新生大鼠海马细胞氧化应激、DNA损伤和凋亡的影响。方法原代培养的新生大鼠海马细胞暴露于10、20、40μg/mlPBDE-47,每组3个平行样,24h后,检测乳酸脱氢酶(LDH)漏出率,细胞内丙二醛(MDA)和还原型谷胱甘肽(GSH)含量、超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)活力、活性氧(ROS)水平以及DNA损伤和细胞凋亡情况。结果与对照组比较,20和40μg/ml组LDH漏出率升高,差异有统计学意义(P<0.05)。各染毒组MDA含量均高于对照组,GSH-Px活力均低于对照组,且20和40μg/ml组与对照组比较,差异均有统计学意义(P<0.05);10、20、40μg/ml组GSH含量和SOD活力均低于对照组,差异有统计学意义(P<0.05),但各染毒组之间差异无统计学意义(P>0.05);20和40μg/ml组细胞内ROS水平高于对照组,差异均有统计学意义(P<0.05)。10、20、40μg/ml组尾部DNA百分率和Oliver尾矩均高于对照组,差异均有统计学意义(P<0.05);20和40μg/ml组细胞凋亡率均高于对照组,差异有统计学意义(P<0.05),且呈上升趋势。相关分析表明,海马细胞DNA损伤、凋亡百分率与ROS水平呈正相关(r值分别为0.982,0.998,P<0.05),细胞凋亡百分率与DNA损伤呈正相关性(r=0.967,P<0.05)。结论PBDE-47可致原代新生大鼠海马细胞氧化应激和诱导细胞DNA损伤和凋亡,呈现一定的神经毒性。Objective To investigate the effects of polybrominated diphenyl ethers （PBDE-47） on oxidative stress, DNA damage, and apoptosis in primary rat hippocampal neurons. Methods LDH leakage, contents of MDA and GSH, activities of SOD and GSH-Px, ROS level, DNA damage and apoptosis were measured respectively after the rat hippocampal neurons were exposed to 10, 20, and 40 μg/ml PBDE-47 for 24 h in vitro. Results The LDH leakages in the middle and high PBDE-treated groups （20, 40 μg/ml） were significantly higher than that in control group and increased with increasing PBDE-47 concentrations. The MDA content was higher, while the activity of GSH-Px was decreased and there was a significant difference in the middle and high PBDE-treated groups （20, 40μg/ml） as compared to control group （P〈0.05）. Compared with the control group, the GSH content and SOD activity were significantly lower, but no statistic differences were shown among the PBDE-treated groups （10, 20, 40 μg/ml）. Significant difference on the ROS level was seen in the middle and high PBDE-treated groups （20, 40 μg/ml） in contrast to the control group （P〈0.05）. DNA tail moment and percentage of DNA in the tail were higher in the all PBDE-treated groups than that in control group. Compared with the control group, there was an appreciable increase in the percentage of apoptotic cells in the middle and high PBDE-treated groups （20, 40 μg/ml）. There existed positive correlations between ROS level and DNA damage（r=0.982, P〈0.05）, apoptosis（r=0.998, P〈0.05）. And there was a positive correlation between DNA damage and apoptosis （r=0.967, P〈0.05）. Conclusion PBDE-47 can induce oxidative stress, DNA damage and apoptosis in primary rat hippocampal neurons. All data are shown that PBDE-46 has potential neurotoxicity in vitro.

关 键 词：DNA损伤 2 2’ 4 4’-四溴联苯醚 氧化应激 细胞凋亡 

分 类 号：R994.6[医药卫生—毒理学]