北华大学学报（自然科学版）2017，Vol.18Issue(1)：46-49,4.DOI:10.11713/j.issn.1009-4822.2017.01.010
依折麦布对高迁移率族蛋白1诱导血管内皮细胞激活的影响机制研究
Effect Mechanism of Ezetimibe on High Mobility Group Box-1 Protein-Induced Activation of Vascular Endothelial Cell
摘要
Abstract
Objective To investigate the molecular effect mechanism of ezetimibe on high mobility group box-1 protein ( HMGB1 )-induced activation of vascular endothelial cells. Method Male SD rats ’ thoracic aorta endothelial cells were separated and cultured, which were randomly divided into blank control group, HMGB1 stimulation group,ezetimibe group ( pre-treated with 10 μmol/L ezetimibe before HMGB1 stimulation) ,and CLI-095 group ( pre-treated with 1 μmol/L CLI-095 before HMGB1 stimulation ) . Fluorescence quantitative analysis was applied to analyze the adhesion of neutrophils to endothelial cells;RT-PCR and Western blot were used to detect TLR4 , ICAM-1, soluble E-selectin mRNA and protein expression levels in endothelial cells;the DNA binding activity of NF-κb p65 was tested by EMSA assay. Results Adhesion activities of HMGB1-activated endothelial cells to the polymorphonuclear cells were significantly higher than those in the blank control group ( P<0 . 05 );adhesion activities of CLI-095 group endothelial cells to the polymorphonuclear cells in ezetimibe group were significantly lower than those in HMGB1-induced group (P<0. 05). The expression of TLR4,mRNA and protein in endothelial cells in HMGB1 stimulation group was significantly higher than that in the control group ( P<0 . 05 );mRNA and protein expressions in endothelial cells in ezetimibe group and CLI-095 group were significantly lower than those in HMGB1 group ( P<0 . 05 ) . The nuclear shift of NF-κb p65 subunit of endothelial cells in HMGB1 group was greater than that in the blank control group ( P<0 . 05 );the nuclear shift in ezetimibe group and CLI-095 group was significantly weakened compared with that in HMGB1 group (P<0. 05). The expression levels of ICAM-1 and soluble E-select in HMGB1 group were significantly higher than those in the blank control group (P<0. 05),and the ezetimibe and CLI-095 intervention could significantly reduce the ICAM-1 and soluble E-selectin mRNA expression compared with HMGB1 group ( P<0. 05 ). Conclusion Ezetimibe can effectively inhibit the activation of HMGB-induced vascular endothelial cells by regulating the expression of adhesion molecules (ICAM-1 and soluble E-selectin),and the mechanism may be related to its inhibition on the expression of TLR4 and the activation of NF-κb.关键词
高迁移率族蛋白1/依折麦布/血管内皮细胞/TLR4Key words
HMGB1/ezetimibe/vascular endothelial cells/TLR4分类
医药卫生引用本文复制引用
付建平,袁兰所,牟丽娜,郑群..依折麦布对高迁移率族蛋白1诱导血管内皮细胞激活的影响机制研究[J].北华大学学报（自然科学版）,2017,18(1):46-49,4.基金项目
河北省卫生厅科研基金项目(2015C0861) （2015C0861）
