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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。
Objective To study the changes of hepatic membrane transport protein multidrug resistance associated protein 2 (MRP2) in arsenism rats and its effects. Methods Thirty healthy Wistar rats were randomly divided into 6 groups: 2 weeks exposure group, 4 weeks exposure group, 6 weeks exposure group, and 3 control groups. With sodium arsenite 20mg kg body weight intragastrically, every other day. Determination of Total Arsenic in Bile and Whole Blood by Atomic Absorption Spectrophotometry. The content of MRP2 on the membrane of hepatocyte was detected by Western blotting. Results During the exposure period, total arsenic in whole blood and bile was significantly higher than that in the control group (P <0.05). In particular, excretion of bile arsenic was more obvious at the second and fourth weeks of exposure, which were respectively 16 .8 and 13.8 times. The expression of MRP2 increased (P <0.05 compared with the control group at the same period), and increased by 36.61%, 32.36% and 12.73% from the second week to the sixth week respectively. The expression of MRP2 was positively correlated with the content of bile arsenic (r = 0.73, P <0.05). Conclusion Bile is one of the important pathways of excretion of arsenic and its metabolites. The increased expression of transporter MRP2 on hepatocyte membrane may play an important role in promoting bile excretion of arsenic and its metabolites early.