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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。
OBJECTIVE: To investigate the effect of geniposidic acid (GPA) on multidrug resistance-associated protein 2 (MRP2) and bile acid transport in BRL-3A cells by silencing farnesyl ester derivative X receptor (siRIFN) Bile salt output pump (BSEP). Methods: The effects of si RNA-mediated FXR silencing and GPA on FXR, MRP2 and BSEP gene expression in BRL-3A cells were detected by RT-PCR. Western blot was used to detect the FXR silencing in BRL-3A cells after GPR was silenced Or not, on the protein levels of FXR, MRP2 and BSEP. Results: GPA at concentrations of 4mmol / L and 1mmol / L upregulated the mRNA and protein expression of FXR, MRP2 and BSEP in BRL-3A cells, and was positively correlated with the dosage of GPA. There was a statistically significant difference (P < 0.01, P <0.05). GPA at concentrations of 4 mmol / L and 1 mmol / L reversed the decrease of gene and protein levels of FXR, MRP2 and BSEP induced by si RNA-FXR silencing 0.05), and the dose was positively related to GPA. CONCLUSION: Silencing FXR can down-regulate the expression of MRP2 and BSEP gene and protein in bile acid transporters. GPA up-regulates the expression of MRP2 and BSEP gene and protein in vitro by up-regulating FXR.