【摘要】 目的:通过si RNA干扰法尼酯衍生物X受体(FXR)基因沉默与否考察京尼平苷酸(GPA)对BRL-3A细胞中多药耐药相关蛋白2(MRP2)和胆汁酸转运体胆盐输出泵(BSEP)的影响。方法:运用RT-PCR检测si RNA介导FXR沉默结果和GPA对BRL-3A细胞中FXR、MRP2和BSEP基因水平的影响;Western blot检测FXR被沉默后、以及GPA对BRL-3A细胞中FXR沉默与否,对FXR、MRP2和BSEP蛋白水平的影响。结果:4mmol/L和1mmol/L浓度的GPA可以上调BRL-3A细胞中FXR、MRP2和BSEP基因和蛋白的表达水平,且与GPA的剂量呈正相关,在统计学上有显著性差异(P<0.01,P<0.05);4mmol/L和1mmol/L浓度的GPA可以逆转因si RNA-FXR沉默引起的FXR、MRP2和BSEP基因和蛋白水平降低,差异有统计学意义(P<0.01,P<0.05),且以GPA呈剂量正相关。结论:FXR的沉默可下调胆汁酸转运体MRP2和BSEP基因和蛋白的表达,GPA在体外可通过上调FXR来上调MRP2和BSEP基因和蛋白的水平。更多还原

【Abstract】 Objective: To investigate the effects of geniposidic acid(GPA) on the protein expression of multidrug resistance protein 2(MRP2) and bile salt export pump(BSEP) in BRL-3A cells, which was mediated by small interfering RNA(si RNA) farnesoid X receptor(FXR) gene silencing. Methods: RT-PCR was used to detect the result of FXR gene silencing and the gene levels of FXR, MRP2 and BSEP in BRL-3A cells affected by GPA, and Western blot was used to detect whether FXR gene silencing in BRL-3A cells or not by GPA and the protein expressions of FXR, MRP2 and BSEP in BRL-3A cells induced by geniposidic acid. Results: Compared with control group, the levels of m RNA and protein expressions of FXR, MRP2 and BSEP in BRL-3A cells were significantly increased in GPA group with the concentration of 4mmol/L and 1mmol/L(P<0.01, P<0.05). GPA with concentration of 4mmol/L and 1mmol/L could significantly reverse the levels of m RNA and protein expression of FXR, MRP2 and BSEP in BRL-3A cells(P<0.01, P<0.05), which was mediated by si RNA-FXR. Conclusion: FXR gene silencing could down-regulate the levels of m RNA and protein expression of MRP2 and BSEP, and the GPA could up-regulate FXR to upregulate the levels of m RNA and protein expression of MRP2 and BSEP.更多还原