目的探讨低剂量二噁英慢性暴露对雄性大鼠血清蛋白表达的影响,进一步加深对二噁英毒性机制的理解。方法将32只6周龄雄性SD大鼠随机分为高、中、低2,3,7,8.四氯二苯并二噁英(TCDD)剂量组(染毒剂量分别为875、350和140ng/kg)和对照组(仅给玉米油),每周一次,灌胃染毒29周。染毒结束后,采用双向凝胶电泳-质谱分析-生物信息学检索的经典技术路线,对二噁英暴露后血清蛋白表达谱进行分析;同时进行肝脏组织形态学检查。结果与对照组相比,二噁英导致大鼠肝脏明显的脂肪变性和坏死;二噁英暴露后触珠蛋白表达下调,载脂蛋白E表达上调,胎球蛋白类蛋白仅在高剂量组表达。结论二噁英暴露对大鼠血清蛋白表达产生了一定的影响,所鉴定的差异蛋白可作为潜在的毒性标志物,有助于二噁英毒性机制的理解。
Objective To explore the chronic effect of low levels of 2, 3, 7, 8-tetraehlorodibenzo-p-dioxin (TCDD) exposure on the protein expression profile in the serum of rats and to get the further understanding of the molecular mechanism of TCDD toxicity. Methods Thirty-two male SD rats were randomly divided into three TCDD exposed groups treated with TCDD at the doses of 875, 350 and 140 ng/kg by gavage, once a week, for 29 consecutive weeks respectively and one control group treated with single corn oil. The proteins in the serum were separated and analyzed by two-dimensional gel eleetrophoresis and mass spectrometry, the histopathologieal examination of livers was performed at the same time. Results TCDD induced significant fatty degeneration and necrosis in the livers. Several interesting volume-altered protein spots were identified. Among these proteins, Bal-647 was down- regulated, apolipoprotein E was up-regulated by TCDD and fetuin-like protein was only expressed in the group of 875 ng/kg, Conclusion The differentially expressed proteins may contribute to a better understanding of the toxicity induced by TCDD and may be used as the biomarkers of effect for TCDD exposure.