The Effect Of Atorvastatin On The Expression Of LXRα And Its Target Genes, Inflammatory Factors And Adhesion Factors In Human Umbilical Vein Endothelial Cells After Treated By Lipopolysaccharide

Objective: The cultured human umbilical vein endothelial cells(HUVECs) were stimulated with lipopolysacharide (LPS) to imitate an inflammation state in vitro. To investigate the effects of atorvastatin or LXR agonist T0901317 or both on LPS-induced gene expression (eg,liver X receptor and its target genes ABCA1,SREBP-1,inflammatory factor Interleukin 6, Intercellular adhesion molecule-1, Platelet endothelial cell adhesion molecule-1) in human umbilical vein endothelial cells and discuss the clinical significance.Methods:HUVECs were cultured with Gibco 1640 medium which contain 10% fetal bovine serum,1% double antibiotics (streptomycin/penicillin),and then were plated in 6-well plates at a denisity of approximately 2×105 cells per milliliter of media to be invervention. 1.LPS inventration group :control group:the HUVECs were cultured with the completed medium involving PBS; and LPS treated group:the HUVECs were treated with LPS (the terminal concentration was 100 ng/ml) for 24 hours; 2.Atorvastatin inventration group:the HUVECs were first treated with atorvastatin at different concentrations (0.1,1,10μmol/L) or DMSO for 2 hours, and then co-treated with LPS for 22 hours; 3.LXR agonist T0901317 inventration group:the HUVECs were first treated with LXR agonist T0901317 (the terminal concentration was 1μmol/L) or DMSO for 2 hours, and then co-treated with LPS for 22 hours; 4.Atorvastatin and T0901317 co-inventration group:the HUVECs were treated with atorvastatin or T0901317 or both for 2 hours,and then co-treated with LPS for 22 hours Cells were harvested after cultivation with different intervention for 24 hours. Total RNA was abstracted by TRIzol reagent,and then reverse transcription the RNA to cDNA. The level of LXRαand its target genes inflammation factor and adhesion factors mRNA expression were measured by real-time polymerase chain reaction.Results:Compared with conrol group, LPS can inhibit the mRNA expression of LXRαand its target genes ABCA1,SREBP-1, and increase IL-6.ICAM-1 and PECAM-1 mRNA expression in HUVECs. Atorvastatin can upregulate the mRNA expression of LXRa and its target gene, and downregulate IL-6,ICAM-1 and PECAM-1 mRNA expression in a dose-dependent manner. Meanwhile, T0901317 can obviously up-regulated LXRα, ABC A1 and SREBP-1 mRNA expression, and reduce IL-6,CAM-1 and PECAM-1 mRNA expression.Furthermore, the combined application of atorvastatin and T0901317 exert more beneficial effects.Conclusion:1.LPS may inhibit the mRNA expression of LXRαand its target genes in HUVECs; 2.Atorvastatin may inhibit the inflammation state of endothelial cells, the possible mechanism may be mediated partly through LXR signal pathway;3.LXR agoinst T0901317 may improve the fuction of vascular endothelial cell;4.Atorvastatin and LXR agonist have a synergistic effect on inhibiting inflammation in endothelial cells.