不同剂量亚砷酸钠染毒大鼠多药耐药相关蛋白2表达水平的变化

Expression of multidrug resistance-associated protein 2 in rats administrated with different concentrations of sodium arsenite

目的观察不同剂量亚砷酸钠染毒大鼠肝细胞膜转运蛋白——多药耐药相关蛋白2(multidrugresistance-associatedprotein2,MRP2)表达水平的变化及与砷代谢的关系。方法24只健康雄性Wistar大鼠随机分为4组:第1组为对照组,给予生理盐水;第2～4组为染砷组,分别给予4、10和20mg/kg体质量的亚砷酸钠溶液,隔天灌胃染毒1次,2周后将大鼠处死。原子吸收分光光度法测定胆汁、全血和肝组织中的总砷含量。蛋白印记法测定肝细胞膜上MRP2的改变。结果经方差分析检验,胆汁和肝脏中含砷量随着染砷剂量的增加而逐渐增加(P<0.05)。两两比较发现,3个染毒组的血砷与对照组之间差异有统计学意义,而3个染毒组间差异无统计学意义。随着染砷剂量增加,MRP2表达有增加的趋势,且MRP2表达量与胆汁含砷量呈正相关(r=0.986,P<0.05)。结论亚砷酸钠可以诱导MRP2的表达,随染砷剂量增加,MRP2表达量增加。MRP2在砷及其代谢产物的胆汁排泄过程中发挥了重要作用。

Objective To explore the relationship between the expression of hepatic multidrug resistance- associated protein 2 （MRP2）in rat correspondence with arsenite and arsenite metabolites. Methods Twenty-four healthy male Wistar rats were divided randomly into four groups and administrated with different concentrations of sodium arsenite ： 0, 4, 10 and 20 mgAs^＋3/kg BW every the other day for two weeks. Animals were sacrificed two weeks later. Arsenic content in bile, blood and liver were detected by atomic absorption spectroscopy （AAS）, and the expression of MRP2 in the membrane of hepatocyte was determined by Western-blot analysis. Results The level of total arsenic （including organic arsenic and inorganic arsenic） in blood, bile and liver of three different dose groups were higher than those in control groups （P 〈 0.05）. Arsenic levels of bile and liver increased with arsenic dose intragastrically administered Blood arsenic levels were not significantly different in three different dose groups. Expression of hepatic MRP2 increased along with the increased arsenic concentration of intragastric administration. A positive correlation between biliary arsenic concentration and MRP2 levels was found in liver （r = 0.986,P 〈 0.05）. Conclusions Sodium arsenite can induce the expression of MRP2, the up-regulation of MRP2 may play an important role in the bile secretion of arsenite and its metabolites.