氧化性低密度脂蛋白对肝细胞脂肪积累及SIRT1-LXR信号通路的影响

目的探讨氧化性低密度脂蛋白（αLDL）对肝细胞内脂肪积累及SIRT1-LXR信号通路的影响。方法实验分为对照组、高脂（HF）组、αLDL组、HF＋αLDL组和能量限制（CR）组。将HepG2细胞培养于DMEM培养基中，培养48h后用油红O染色法定性观察和测定各组OD值、细胞内脂肪积累，并用RT—PCR法检测各组SIRT1、肝x受体（LXR）及其靶基因ATP结合盒转运蛋白G1（ABCG1）的表达水平。结果与对照组比较，HF组、αLDL组和HF＋αLDL组细胞内脂肪含量均增加（P〈0．05），CR组脂肪含量下降（P〈0．05）。αLDL组与对照组比较，SIRT1、LXRct和ABCG1mRNA表达均增加，其中SIRT1和LXRα差异有统计学意义：HF组SIRT1和LXRα表达与对照组比较差异无统计学意义（P〉0．05），而ABCG1显著降低（P〈0．05）；HF＋αLDL组LXRα和ABCG1表达均显著降低（P〈0．05），而SIRT1与对照组比较差异无统计学意义；CR组LXRα和ABCG1表达均显著增加（P〈0．05），然而SIRT1与对照组比较差异无统计学意义。结论αLDL可能会促进脂肪肝的形成。

Effects of oxLDL on fat accumulation and activity of SIRT1-LXR signaling in HepG2 cells

Objective To investigate the effect of oxidized LDL （oxidized low density lipoprotein,oxLDL） on the fat accumulation and gene expression of SIRT1-LXR signaling in HepG2 cells. Methods HepG2 cells were cultured in DMEM medium. Cells were divided into 5 groups： the control, high fat（HF）, oxLDL, HF＋oxLDL and calorie restriction （CR）groups. The fat accumulation was qualitatively and quantitatively analyzed in cells by using oil red O staining method. RT-PCR was used to detect the mRNA expression of SIRT1, LXRα （liver X-activated receptor） and ABCG1 （ATP-binding cassette transporter Gl,a target of LXRoL） gene in HepG2 cells after 48h culture. Results The fat accumulation significantly increased in the HepG2 cells of the HF, oxLDL and HF＋oxLDL groups compared with the control group （all P〈0.05）, whereas the fat accumulation in CR group was decreased （P〈0.05）. The mRNA expression of SIRT1, LXRot and ABCG1 were up-regulated in the oxLDL group, in which SIRT1 and LXRα had statistical differences compared with those of the control group. The expression levels of SIRT1 and LXRα in the HF group were comparable with the control, however, ABCG1 expression was significantly decreased （P〈0.05）. In the HF＋αLDL group, LXRα and ABCG1 expression was significantly decreased, whereas, SIRT1 expression did not show statistical difference with that of the control. In contrast, the expression of LXRα and ABCG1 was significantly increased, although SIRT1 expression level did not show statistical difference when compared with that of the control. Conclusion Our results suggest that oxLDL may promote the fatty liver formation.