胆红素拮抗间二硝基苯致大鼠肝细胞DNA氧化损伤作用  

The Antagonistic Effect of Bilirubin Against the m-DNB Induced Oxidative Stress,DNA Damage and Synthesis Inhibition in Primary Culture Rat Hepatocyte

作　　者：王天成[1] 贾光[2] 王起恩[2] 张金华[2] 韩春华[2] 程有全[2] 沈惠麒[2] 

机构地区：[1]北京大学第三医院检验科,北京100083 [2]北京大学公共卫生学院劳动卫生与环境卫生学系,北京100083

出　　处：《环境与职业医学》2006年第5期393-395,共3页Journal of Environmental and Occupational Medicine

摘　　要：[目的]探讨胆红素拮抗间二硝基苯(m-DNB)诱导大鼠肝细胞DNA氧化损伤作用。[方法]原代培养大鼠肝细胞与不同剂量m-DNB孵育,细胞色素C还原法和电子顺磁自旋捕获法观察m-DNB染毒大鼠肝细胞超氧阴离子自由基()和羟自由基(OH?)生成;以单细胞凝胶电泳和氚胸腺嘧啶(3H-TdR)掺入法分别观察m-DNB对大鼠肝细胞DNA损伤和合成抑制情况,分析胆红素干预对以上情况的影响。[结果]随m-DNB剂量增加,大鼠肝细胞和OH?水平、DNA受损细胞数和细胞DNA断裂程度增加,3H-TdR掺入量下降,具有较明显的剂量-反应关系(P<0.01)。10μmol/L胆红素干预可明显减低m-DNB致大鼠肝细胞和OH?水平、降低DNA受损细胞数和细胞DNA断裂程度、拮抗m-DNB对大鼠肝细胞DNA合成的抑制(P<0.01)。[结论]胆红素可拮抗m-DNB诱导大鼠肝细胞活性氧导致的DNA氧化损伤、减轻m-DNB对大鼠肝细胞DNA合成的抑制作用。[ Objective ] To study the effects of bilirubin on the oxidative DNA damage induced by m-dinitrobenzene （ m-DNB ） in primary culture of rat hepatocyte. [ Methods ] Inhibition of O2^- by bilirubin and OH° generation on rat hepatocyte induced by m-DNB were determined by cytochrome C reduction and ESR assay. The antagonistic effect of bilirubin on rat hepatocyte DNA injury and synthesis inhibition induced by m-DNB were determined by single cell electrophoresis and 3H-TdR incorporation method. [ Results ] m-DNB may induce rat hepatocyte O2^- and OH° generation, DNA injury and synthesis inhibition significantly in a dose-dependent manner; bilirubin may obviouly depress the O2^- and OH° production, attenuate DNA damage and synthesis inhibition in rat hepatocyte induced by m-DNB. [ Conclusion ] Bilirubin may play a protective role on rat hepatocyte exposed to m-DNB by means of eliminating O2^- and OH°, decreasing oxidative DNA injury and inhibiting DNA synthesis.

关 键 词：胆红素 抗氧化 间二硝基苯 DNA损伤 

分 类 号：R114[医药卫生—卫生毒理学]