法尼酯X受体上调载脂蛋白F在肝细胞中的表达

Farnesoid X receptor upregulates apolipoprotein F expression in cultured liver cells

目的研究法尼酯X受体(farnesoid X receptor,FXR)的激活在肝细胞中对载脂蛋白F(apolipoprotein F,ApoF)基因表达的影响。方法应用逆转录-聚合酶链反应(RT-PCR)法和Western blot检测不同浓度鹅脱氧胆酸(chenodeoxy cholic acid,CDCA,0、25、50、100μmol/L)和人工合成FXR配体GW4064(0、0.02、0.2、2μmol/L)处理后HepG2和L02细胞中的小分子异二聚体伴侣(small heterodimer partner,SHP)及ApoF的mRNA和蛋白水平变化。结果结果①经FXR天然配体CDCA处理24 h后,不同浓度处理组细胞SHP mRNA水平、ApoF mRNA和蛋白水平均显著高于未处理组(P<0.05)。②经FXR人工合成配体GW4064处理24 h后,不同浓度处理组细胞SHP mRNA水平、ApoF mRNA和蛋白水平均显著高于未处理组(P<0.05)。结论肝细胞株HepG2和L02经FXR配体CDCA或GW4064处理后,FXR被激活,并上调ApoF的mRNA和蛋白水平。

Objective To determine the effect of farnesoid X receptor（FXR） on the expression of apolipoprotein F（ApoF） in human hepatoblastoma HepG2 cells and hepatocyte L02 cells.Methods After HepG2 cells and L02 cells were treated with FXR agonist chenodesoxycholic acid（CDCA） at 0,25,50 or 100 μmol/L,or with another agonist GW4064 at 0,0.02,0.2,or 2 μmol/L respectively,the mRNA expressions of FXR specific target gene small heterodimer partner（SHP） and ApoF were detected by reverse transcription polymerase chain reaction（RT-PCR）.The apolipoprotein F protein level was determined by Western blotting.Results After treated with CDCA for 24 h,the mRNA levels of SHP and ApoF in the treated cells were significantly higher than the untreated cells（P0.05）,so did the protein expression of ApoF（0.884±0.091 vs 0.185±0.030,P0.05）.After treated with GW4064 for 24 h,the SHP and ApoF expressions at mRNA level were significantly increased in the treated cells than the untreated cells（P0.05）,so did the protein expression of ApoF（P0.05）.Conclusion After the treatment of CDCA and GW4064,FXR is activated in HepG2 cells and L02 cells,which upregulates the expression of apoF.