丹皮酚对HepG2细胞MRP2表达和功能的影响

Effects of Paeonol on expression and function of drug transporters MRP2 in HepG2 cells

目的:研究丹皮酚对人肝细胞株Hep G2细胞中多药耐药相关蛋白2(multidrug resistance-associated protein 2,MRP2)表达及功能的影响,以探讨丹皮酚消退黄疸的作用机制。方法:采用CCK8法检测丹皮酚对Hep G2细胞存活率的影响;q PCR法测定丹皮酚对Hep G2细胞MRP2和PXR m RNA表达水平的影响;流式细胞术测定丹皮酚干预后细胞内CDFDA的荧光强度。结果:丹皮酚(2μg/ml)对Hep G2细胞存活率影响较小;丹皮酚在实验条件下明显上调MRP2药物转运体和PXR在转录水平的表达,并增加其对MRP2特异性荧光底物的转运效率(P=0.000)。结论:丹皮酚可能通过上调PXR诱导Hep G2细胞药物转运体MRP2基因表达,从而促进其底物的跨膜转运。提示丹皮酚上调MRP2转运体表达而起到降黄的临床作用可能与核受体PXR途径相关。

Objective：To investigate influences of Paeonol on mRNA expression and function of drug transporters multidrug resistanceassociated protein 2（MRP2）in Hep G2 cell. Methods：Cell counting Kit-8 assay was used to detect the viability of Hep G2 cells. Realtime fluorescent quantitative PCR（q PCR）was performed to measure the expressions of MRP2 and PXR. Flow cytometry was applied to determine the transport function of MRP2. Results：Paeonol（2 μg/ml）did not decrease Hep G2 cell survival rate. Paeonol（2 μg/ml）markedly induced the expression and function of drug transporters MRP2（P=0.000）and the expression of PXR. Conclusion：Paeonol can up-regulate the expression of MRP2 mRNA through the PXR,which may be one of processes of eliminating jaundice.