法尼酯X受体可下调肝细胞中肝型脂肪酸结合蛋白的表达

Farnesoid X receptor down-regulates expression of liver fatty acid-binding protein in liver cells

目的研究法尼酯X受体(farnesoid X receptor,FXR)对肝型脂肪酸结合蛋白(liver fatty acid-binding pro-tein,L-FABP)表达的影响。方法用终浓度为50、100μmol/L的鹅脱氧胆酸(chenodesoxycholic acid,CDCA)以及1、5μmol/L的GW4064分别处理人胚胎肝细胞LO2和人肝癌细胞株HepG2后,用逆转录-聚合酶链反应(RT-PCR)法检测FXR特异靶基因小异二聚体配体(small heterodimer partner,SHP)和L-FABP mRNA表达,再用Western blot法检测L-FABP蛋白水平的变化。结果LO2和HepG2细胞经FXR特异性激动剂CDCA以及GW4064刺激后,细胞内的SHP mRNA水平均明显升高,表明FXR在这两种细胞中是有功能活性的;而L-FABP mRNA和蛋白水平显著下降(P<0.05)。结论激活后的FXR可抑制L-FABP的表达活性。

Objectives To investigate the effect of farnesoid X receptor （FXR） on the expression of liver fatty acid-binding protein （L-FABP）. Methods Human hepatoblastoma HepG2 cells and hepatocyte LO2 cells were treated with FXR agonists chenodesoxyeholic acid （CDCA） at 50 and 100 umol/L or GW4064 at 1 and 5 umol/L respectively. The L-FABP and the specific gene of FXR-small heterodimer partner （SHP） were detected by reverse transcription polymerase chain reaction （RT-PCR）. The L-FABP protein level was determined by Western blotting. Results After treated with CDCA or GW4064, SHP mRNA level in HepG2 and LO2 was increased obviously, which suggested FXR was functional in those cells. The mRNA and protein levels of L-FABP was decreased dramatically in those cells （ P 〈 0.05 ）. Conclusion Farnesoid X receptor downregulates the expression of L-FABP in hepatocytes.