苯对小鼠骨髓单个核细胞多药耐药基因1和P-糖蛋白表达的影响  

The effects of benzene poisoning on expression of multidrug resistance 1 gene and P-glycoprotein in bone marrow mononuclear cells of C57BL/6 mice

作　　者：黄简抒[1] 史继敏[2] 张继红[2] 李炳[2] 范卫[2] 周元陵[1] 

机构地区：[1]复旦大学附属金山医院核化伤害救治中心职业病科,上海200540 [2]复旦大学附属金山医院中心实验室,上海200540

出　　处：《中华劳动卫生职业病杂志》2013年第1期14-18,共5页Chinese Journal of Industrial Hygiene and Occupational Diseases

基　　金：国家自然科学青年基金（81202160）;上海市卫生局青年基金（2012-167）;复旦大学医学院青年骨干科研启动基金（10L-35）

摘　　要：目的探讨苯染毒对C57BL／6小鼠骨髓单个核细胞多药耐药基因1（multidrugresistance1，MDR1）基因和P．糖蛋白（P-glycoprotein，P-gP）表达的影响。方法实验动物随机分为对照组、低剂量组、中剂量组、高剂量组，每组24只，分别以单纯玉米油及25、50、100mg＆g剂量苯灌胃染毒C57BL／6小鼠，每日1次，每周5次，连续染毒4周，染毒12、26、29d后分批处死小鼠，检测C57BL／6小鼠外周血常规，实时定量PCR检测骨髓单个核细胞MDR1基因表达，免疫印迹法检测骨髓单个核细胞的P-gP表达。结果染毒12d，高剂量组红细胞、血红蛋白明显低于对照组、低剂量组、中剂量组，差异有统计学意义（P〈0．01、P〈0．05）。染毒26d，高剂量组白细胞明显低于对照组、低剂量组、中剂量组，差异有统计学意义（P〈0．01、P〈0．05）。各时间点各染毒组的MDR1基因mRNA表达均明显低于对照组，差异均有统计学意义（P〈0．01）。染毒26d，高剂量组P-gP表达低于对照组、低剂量组和中剂量组，中剂量组P-gP表达低于低剂量组，差异均有统计学意义（P〈0．01、P〈0．05）；染毒29d，各染毒组P-gP表达均低于对照组，差异均有统计学意义（P〈0．05）。结论苯染毒干扰骨髓单个核细胞MDR1基因和P-gP表达，可能是苯血液毒性的机制之一。Objective To investigate the effects of benzene poisoning on the expression of muhidrug resistance 1 （MDR1） gene and P-glycoprotein （P-gp） in the bone marrow mononuclear cells （BMMNCs） of C57BL/6 mice. Methods C57BL/6 mice were randomly divided into control group （n=24）, low-dose group （n=24）, medium-dose group （n=24）, and high-dose group （n=24） to receive corn oil, 25 mg/kg benzene, 50 mg/kg benzene, or 100 mg/kg benzene by garage, once daily, 5 days/weeks, for 4 weeks. The mice were sacrificed on day 12, 26, or 29 of poisoning. Peripheral blood routine test was performed; real-time quantitative PCR was used to measure the MDR1 gene expression in BMMNCs; Western blot was used to measure the P-gp expression in BMMNCs. Results On day 12, the red blood cell count and hemoglobin level in the high-dose group were significantly lower than those in the control group, low-dose group, and medium-dose group （P〈0.01 or P〈0.05）. On day 26, the white blood cell count in the high-dose group was significantly lower than those in the control group, low-dose group, and medium-dose group （P〈0.01 or P〈0.05）. At each time point, the mRNA expression of MDR1 gene in the low-dose group, medium-dose group, and high-dose group was significantly lower than that in the control group （P〈0.01）. On day 26, the P-gp expression in the high-dose group was significantly lower than those in the control group, low-dose group, and medium-dose group, and the P-gp expression in the medium-dose group was significantly lower than that in the low-dose group （P〈0.01 or P〈 0.05）. On day 29, the P-gp expression in the low-dose group, medium-dose group, and high-dose group was significantly lower than that in the control group （P〈0.05）. Conclusion Benzene poisoning can affect the expression of MDR1 gene and P-gp, which may be one of the mechanisms of benzene hematotoxicity.

关 键 词：苯 骨髓单个核细胞 MDR1基因 P-糖蛋白 

分 类 号：R1[医药卫生—公共卫生与预防医学]