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OALib Journal期刊
ISSN: 2333-9721
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基于rna干扰技术的外排转运体体外模型及评价
, PP. 1122-1127
Keywords: rna干扰,小干扰rna,p-糖蛋白,多药耐药相关蛋白2
Abstract:
为建立多药耐药相关蛋白2(mrp2)和p-糖蛋白(p-gp)的体外rna干扰模型,应用化学合成的sirna转染hepg2细胞,并用实时pcr和westernblot检测mrna和蛋白的表达变化,应用mrp2和p-gp底物罗丹明和甲氨蝶呤进行功能评价确定模型是否成功。sirna筛选结果显示,mrp2sirna-3或p-gpsirna-2能够显著地抑制mrp2或p-gp的mrna表达,抑制率分别为68%和84%;mrp2sirna-3或p-gpsirna-2(80nmol·l-1)作用48h能够明显地抑制mrp2或p-gp的蛋白表达,抑制率分别为62%和70%,同时不影响其他转运蛋白的表达;给予mrp2或p-gp底物甲氨蝶呤或罗丹明孵育,发现mrp2sirna-3或p-gpsirna-2(80nmol·l-1)作用48h能够显著增加甲氨蝶呤或罗丹明的细胞内浓度,表明其外排受到抑制。以上结果表明利用化学合成的sirna能够显著地抑制细胞mrp2和p-gp的表达和功能,提示细胞干扰模型建立成功。
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