环境与职业医学2011，Vol.28Issue(7)：409-413,5.
维生素E对氯化镍染毒大鼠肺组织p15基因甲基化过程的影响
Effects of Vitamin E on the Methylation of pl5 in Lung of Rats Exposed to Nickel Chloride
摘要
Abstract
[Objective]To investigate the effects of vitamin E on the methylation ofpl5 in lung of rats exposed to nickel chloride.[Methods]The rats were fed by gavage with the designed concentrations of NiCl2 ·6H20( 0.1, 0.2, 0.4 and 0.8 mg/mL )for four different exposed groups and 0.9％ NaCl solution for the solvent control group.The antagonism group was supplied with vitamin E ( 5 mg/mL ) along with 0.8 mg/mL NiCl2.After treating the rats for six weeks, we detected the levels of malondialdehyde ( MDA )and glutathione( GSH )to assess oxidative stress in the lung tissues.In addition, we also evaluated the methylation status and expressions of tumor suppressor gene p15 using methylation specific PCR and quantitative real time PER.DNA methyltransferase ( DNMT1 )and methionine adenosyltransferase 2A( MAT2A )that play key role in methylation process were detected by western blot.[Results]Compared with the control group, the levels of MDA in lung of the rats exposed to nickel chloride increased significantly,while the levels of GSH decreased significantly( P＜0.01 ).As compared with the high-dose group( 0.8mg/mL NiCl2 ), a significant increase in GSH contents was observed in the antagonism group( NiCl2+VE ), while the levels of MDA decreased significantly( P＜0.05 ).The tumor suppressor gene ofpl5 was found to be non-methylated in the control group.The methylation and non-methylation ofpl5 were both observed in NiCl2 exposure groups and VE antagonism group.Compared with the control group, the levels of pl5 were down-regulated significantly in the NiCl2 exposure groups( P＜0.01 ).As compared with the high-dose group( 0.8 mg/mL NiCl2 ),a significant increase inpl5 levels was observed in the antagonism group( NiCl2+VE )( P＜0.05 ).The levels of DNMT1 and MAT2A significantly increased as the concentrations of NiCl2 increased, and the ratios increased 1.52- and 1.49- folds in the high-dose group respectively compared with the control group.Compared with the high-dose group, the relative ratios of DNMTl and MAT2A in the antagonism ( NiCl2+VE )group decreased 18％ and 29％ respectively.We found that the levels of GSH were correlated negatively with the relative expressions of DNMT1 ( r=-0.889, P=0.018 )and MAT2A( r=--0.821, P=0.044 ).[Conclusion]Our findings suggest that glutathione influenced by vitamin E may play important role in DNA methylation.关键词
氯化镍/维生素E/甲基化Key words
nickel chloride/ Vitamin E/ methylation分类
医药卫生引用本文复制引用
杨瑾,王志武,刘承芸,郭庆峰,张玲..维生素E对氯化镍染毒大鼠肺组织p15基因甲基化过程的影响[J].环境与职业医学,2011,28(7):409-413,5.基金项目
山西省青年科技研究基金资助项目(编号:2009021044-1) （编号:2009021044-1）
山西省高等学校优秀青年学术带头人支持计划资助(编号:晋教科[2010]4号) （编号:晋教科[2010]4号）
