白藜芦醇及其糖苷白藜芦醇苷与药物外排转运体的相互作用研究

中国临床药理学与治疗学 ›› 2008, Vol. 13 ›› Issue (4): 366-372.

白藜芦醇及其糖苷白藜芦醇苷与药物外排转运体的相互作用研究

何卉, 陈西敬, 王广基

中国药科大学药物代谢研究中心，南京210009,江苏

收稿日期:2008-04-17 修回日期:2008-04-22 出版日期:2008-04-26 发布日期:2020-10-12
通讯作者: 王广基,男,教授,博士生导师,研究方向:药物代谢动力学。Tel:025-83271128
作者简介:何卉,女,博士研究生,研究方向:药物代谢动力学。 E-mail:njhehui@gmail.com

The interaction of Trans -resveratrol and its glucoside Trans peceid with drug transporters

HE Hui, CHEN Xi-jing, WANG Guang-ji

Center of Drug Metabolisn and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, Jiangsu,China

Received:2008-04-17 Revised:2008-04-22 Online:2008-04-26 Published:2020-10-12

摘要/Abstract

摘要： 目的: 通过多种不同细胞模型研究两种芪类天然化合物白藜芦醇(trans-resvenatrol,TR)及白藜芦醇苷(transpiceid,TP)与多种药物外排转运体间的相互作用。方法: 高效液相及荧光分光光度法分别测定细胞内TR.TP及罗丹明123的浓度MTT比色法测定细胞活性,Westemblot法测定P-糖蛋白的表达。结果: P-糖蛋白抑制剂及底物(维拉帕米和罗丹明123)对TR及TP的细胞摄取无影响。多药耐药相关蛋白2抑制剂,丙磺舒可将TR及TP的细胞摄取量分别增加1.3倍和1.6倍。TR及TP能够显著性增加大鼠脑微血管细胞对罗丹朋123的摄取及阿霉素在人白血病阿霉素耐药细胞上的毒性,但对人白血病阿霉素耐药细胞上P-糖蛋白的表达没有显著性改变。米托蔥醌在人非小细胞肺癌细胞.上的毒性作用不受TR及TP的影响。结论: TR及TP可以抑制P-糖蛋白的外排作用,但其本身不被P-糖蛋白外排,而是被多药耐药相关蛋白2外排。TR及TP对人乳腺癌多药耐药蛋白的外排作用没有影响。

关键词: 白藜芦醇, 白藜芦醇苷, 多药耐药相关蛋白, P-糖蛋白, 人乳腺癌耐药蛋白

Abstract: AIM: To study the two stilbenes'(trans resveratrol, TR and its glucoside trans piceid,TP) interaction with A BC transporters in cell models.METHODS: The concentrations of TR，TP， and Rhodimin123 (Rh123) in cells were measured by HPLC or fluorescence spectrophotometer. Cytotoxicity was determined with MTT. The expression of P-gp was evaluated using Westem blot. RESULTS: Pgp's inhibitor and substrate (Verapamil and Rh123) had no impact on the accumulation of the two stilbenes. Pro-benecid, the inhibitor of multidrug resistance -associated protein2 (Mrp-2)，increased accumulation of TR and TP to 1.3 and 1.6 folds. TR andTP increased the uptake of Rh123 in RBMECs. Adriamycin's (ADM) cytotoxicity was also enhanced by the two stilbenes.The expression of Pgp in K562/A02 cells wasn't changed noticeably by∞- incubating with TR or TP.The stilbenes also didn' t change the cytotoxicity of Mitoxantrone (MIT) in Human non -small cell lung cancer cell (NCIH460).CONCLUSION: TR and TP inhibited P-gp from excreting substrates. They were effluent by Mrp2，not P-gp. They didn't affet the effluent of BCRP.

Key words: trans-resveratrol, trans-pecied, multidrug resistance-associated protein, P-gp, breast cancer research program

中图分类号:

R969

何卉, 陈西敬, 王广基. 白藜芦醇及其糖苷白藜芦醇苷与药物外排转运体的相互作用研究[J]. 中国临床药理学与治疗学, 2008, 13(4): 366-372.

HE Hui, CHEN Xi-jing, WANG Guang-ji. The interaction of Trans -resveratrol and its glucoside Trans peceid with drug transporters[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2008, 13(4): 366-372.

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