海胆胚胎不同发育期P-糖蛋白(P-glycoprotein)药物外排功能的研究  

Study of Drug-Efflux Function of P-glycoprotein in Different Developmental Stages of Sea Urchin Embryos

作　　者：孙雪峰[1] 丁君[1] 黄洪辉 王媛[1] 王永华[1] 

机构地区：[1]大连水产学院农业部海洋水产增养殖学重点开放实验室,大连116023 [2]中国水产科学院南海水产研所农业部渔业生态环境重点开放实验室,广州510300

出　　处：《生态毒理学报》2009年第3期428-434,共7页Asian Journal of Ecotoxicology

基　　金：辽宁省创新团队项目(No.2007t017);辽宁省农业攻关计划项目(No.2007203004);辽宁省优秀青年培养计划项目(No.2005203001)

摘　　要：通过研究添加维拉帕米(Verapamil,VER)后,灭蝇胺(Cyromazine)和杀虫丹(Ethiofencarb)对海胆胚胎致死中浓度(LC50)的变化,探讨了不同发育期海胆胚胎P-糖蛋白(P-glycoprotein,P-gp)的功能.结果表明:灭蝇胺和杀虫丹对海胆胚胎的平均LC50分别为2.50mg·L-1和3.50mg·L-1,在加入0.75μmol·L-1P-gp抑制剂VER后,其LC50平均降低40%～42%,说明海胆胚胎P-gp具有药物外排作用.药物浓度可影响P-gp功能,随药物浓度的升高,P-gp外排功能逐渐减弱,甚至达到饱和.实验同时通过分子模拟方法研究了灭蝇胺和杀虫丹的分子结构特征,实验和理论结果均证实了这两种药物分子为海胆胚胎P-gp的底物.The function of P-glycoprotein （P-gp）in different developmental stages of sea urchin embryos was investigated in this work, using cyromazine and ethiofencarb and a P-gp inhibitor verapamil. The average median lethal concentration （LC50）of cyromazine and ethiofencarb were 2.50mg·L^-1 and 3.50mg·L^-1 in different stages, which were reduced by 40% -42% with adding 0.75μmol·L^-1 verapamil. So P-gp in sea urchin embryos has drug-efflux function. The concentration of the pesticides has an important effect on the function of P-gp. The function of P-gp was reduced with the increase of pesticide concentrations, which could get saturation when the pesticide concentration reached a certain value. By molecular modeling methods, the molecular structures of the two compounds were also investigated. Results showed that the two compounds were substrates of P-gp.

关 键 词：P-糖蛋白 海胆胚胎 维拉帕米 灭蝇胺 杀虫丹 

分 类 号：X171.5[环境科学与工程—环境科学] Q256[生物学—细胞生物学]