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

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.

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

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.