山奈酚在HepG2和CaCo2细胞中对MDR1表达的影响以及该影响与PXR之间的关系-药理学(临床药理学)专业论文.docxVIP

ABSTRACTBACKGROUND：P—glucoprotein，which ABSTRACT BACKGROUND：P—glucoprotein，which is encoded by MDRl，is the most important transporter in drug disposition．The phenomenon of mulfidrug resistance is associated with the over-expression of P-glucoprotein．As we all know，P-glucoprotein and CYP3A4 have the similar tissue distribution and a 10t of saine substates．Many inducer of CYP3A4 can induce the expression of P-glueoprotein simultaneously．It has been rep(哦ed that kaempferol call induce CYP3A4 through PXR。 AIMS：Our study is to investigate whether Kaemferol has effect on the expression of MDRl．Also we aim to fred out whether PXR acts in this regulation． METHODS：We treated 0．001I|M、0．OI州、0．1Ⅲ,Vf、1出、5州、109M、 20曲【、50IIM concentrations of kaempferol with HepG2 cells and CaC02 cells respectively and measured the miCrA expression of MDRl by Real—Tune PCR；then we treated CaC02 cells with 20山vl kaempferol for different time to see ff there exsist a time-dependent manner．We also construct PXR transient cotransfection report gene assay in HepG2 cells and CaC02 cells，and treated 0．1州、l州、10州、209M、50州concentrations ofkaempferol谢tll cells respectively，then we got the activity of MDRl promoter by double luciferase detection． RESULTS：The results showed that when we treated HepG2 cells with 10肛M、20pM and 50扯M kaempferol for 24 hours，the mRNA expression of MDRl increased significantly．After 5州、lO洲、20州and 50州 kaempferol were added to CaC02 cells respectively for 24 hours，the mRNA expression of MDRl increased．When We treated CaC02 cells with 20叫vl kaempferol for 12h、24h、48h respectively，the mRNA expression of MDRl were significantly different between the kaempferol group and the vehicle control control group．In the PXR transient cotransfection report gene assay，when we added kaempferol to transfected HepG2 and CaC02 cells for 24 hours，there were no statistical significance between the kaempferol groups and the vehicle control group． CoNCLUSl0NS：Our results showed that kaempferol Can induce