砷对大鼠肝脏多药耐药相关蛋白2影响的研究

目的　研究砷中毒大鼠肝脏膜转运蛋白多药耐药相关蛋白 2 (multidrugresistance associ atedprotein 2 ,MRP2 )表达水平的变化及其作用。方法　 30只健康Wistar大鼠随机分为 6组 :2周染毒组 ,4周染毒组 ,6周染毒组 ,分别设 3个对照组。用亚砷酸钠 2 0mg kg体重灌胃 ,隔天 1次。原子吸收分光光度法测定胆汁中和全血中的总砷含量。蛋白印记法测定肝细胞膜上MRP2的含量改变。结果　染毒期间 ,全血和胆汁中总砷含量明显高于对照组 (P <0 .0 5 ) ,尤其是染毒第 2和第 4周胆汁砷的排泄更加明显 ,分别为对照组的 16 .8和 13.8倍。MRP2的表达增加 (与同期对照组相比 ,P <0 .0 5 ) ,从第 2周到第 6周分别增加 36 .6 1%、32 .36 %、12 .73%。MRP2的表达和胆汁砷的含量呈正相关 (r=0 .713,P <0 .0 5 )。结论　胆汁是砷及其代谢产物排泄的重要途径之一 ,肝细胞膜上的转运蛋白MRP2的表达增加可能在早期促进砷及其代谢产物胆汁排泄中发挥了重要作用。

Toxic effect of arsenite on the expression of liver multidrug resistance-associated protein 2 in rat

Objective To investigate the role of multidrug resistance-associated protein 2(MRP2) in the hepatic cell membrane of rats. Methods Thirty healthy Wistar rats were divided randomly into six groups based on time of administration(2 w,4 w,6 w) of 20 mg/kg of sodium arsenite,and their corresponding control groups.Animals were administered every other day.Arsenic content in blood and bile were detected by atomic absorption spectroscopy(AAS),and the expression of MRP2 in the membrane of hepatocyte by Western blotting was determined. Results Total arsenic levels(including organic arsenic and inorganic arsenic) in blood and bile were significantly higher than control groups(P<0.05) at all three different time points,especially in 2 w and 4 w group(16.8 and 13.8 fold greater than that in control).The expression of MRP2 increased 36.61%,32.36%,12.73% more respectively in 2 w,4 w,6 w groups than those in control groups(P<0.05).The expression of MRP2 was correlated with total arsenic content in bile(r=0.713,P<0.05). Conclusions Bile is one of the major routes for the excretion of arsenite and its metabolites,and the overexpression of MRP2 may play an important role in the bile excretion of them at early stage.