FXR对肝细胞脂质代谢以及Caveolin-1表达的影响

Effect of FXR on Lipid Metabolism and Caveolin-1 Expression in Hepatocytes

【目的】探讨法尼醇x受体（FXR）对肝细胞脂质代谢以及小窝蛋白（Caveolin-1）表达的相关性。【方法】培养肝细胞，分别以10μmol／L的FXR激动剂GW4064和100μmol／L的FXR拮抗剂Guggulsterones干预细胞；RT—PCR和Westernblot检测小异二聚体伴侣（SHP）、胆固醇7α-羟化酶（CYP7A1）、胆盐输出泵（BSEP）的表达；试剂盒检测肝细胞中甘油三酯以及胆固醇的水平；Westernblot检测Caveolin一1的表达。【结果】与对照组相比FXR激动荆组SHP、BSEP、Caveolin-1表达显著升高（P〈0．05），CYP7A1表达显著降低（P〈0．05），FXR拮抗剂组SHP、BSEP、Caveolin-1表达显著降低（P〈0．05），CYP7A1显著升高（P〈0．05）。FXR激动剂组甘油三酯水平显著降低，胆固醇含量显著升高，而FXR拮抗剂组甘油三酯显著升高，胆固醇含量显著降低，差异具有统计学意义（P〈0．05）。【结论】FxR在调控肝细胞代谢中发挥重要作用，并且可能通过对胆固醇代谢的调控影响Caveolin-1的表达。

[Objective] To explore the effect of farnesoid X receptor（FXR） on lipid metabolism and caveolin-1 expression in hepatocytes. [Methods] Hepatocytes were cultured by the treatment with 10/zmol/L FXR agonist GW4064 or 100/~mol/L FXR antagonist guggulsterones, respectively. The expressions of SHP, CYPTA1 and BSEP were detected by RT-PCR and Western blot. The kit was used to determine the levels of triglyceride and cholesterol in hepatocytes. Western blot was used to detect the expression of caveolin-1. [Results]Compared with control group, the expressions of SHP, BSEP and caveolin-1 markedly increased（ P d0.05） and the expression of CYP7A1 markedly decreased in FXR agonist group（ P d0.05）. In FXR antagonist group, the expressions of SHP, BSEP and caveolin-1 in decreased markedly（ P d0.05）, while the expression of CYPTA1 increased marked- ly （ P d0. 05）. Triglyceride level markedly decreased and cholesterol level markedly increased in FXR agonist group, while triglyceride level markedly increased and cholesterol level markedly decreased in FXR antagonist group, and there were significant differences（ P d0.05）. [Conclusion] FXR plays an important role in the regula- tion of hepatocyte metabolism, and may affect the expression of caveolin-I through the regulation of cholesterol metabolism.