中国动脉硬化杂志2018，Vol.26Issue(1)：7-13,7.
依泽替米贝通过上调甾醇调控元件结合蛋白2、低密度脂蛋白受体促进肝细胞摄取低密度脂蛋白胆固醇
Ezetimibe promotes hepatic uptake of low density lipoprotein cholesterol by up-regulating the expressions of sterol regulatory element binding protein-2 and low density lipoprotein receptor
摘要
Abstract
Aim To investigate the effect of ezetimibe on hepatic low density lipoprotein cholesterol (LDLC) uptake and its mechanism.Methods The hyperlipidemia model mice had intragastric administration of 5 mg/(kg · d) ezetimibe.After four months,the contents of total cholesterol (TC),LDLC and high density lipoprotein cholesterol (HDLC) were measured in the blood of mice,and liver tissue morphology was observed by HE staining.HepG2 cells were incubated with ezetimibe (30 μmol/L) and low density lipoprotein (25 mg/L) for 24 hours.The distribution of lipid droplets in cells was observed by oil red O staining.Enzymatic method was used to detect the contents of intracellular TC,free cholesterol (FC) and cholesteryl ester (CE).The uptake of LDLC in cells was detected by DiI-LDL.Realtime fluorescence quantitative PCR and Western blot were used to detect sterol regulatory element binding protein-2 (SREBP-2) and low density lipoprotein receptor (LDLR) expressions at mRNA and protein level,respectively.LDLR content in the hepatic cell membrane was detected by flow cytometry.Results Ezetimibe reduced the content of TC and LDLC in the plasma of mice,increased the content of HDLC and reduced the lipid deposition in liver.Ezetimibe enhanced the ability of HepG2 cells to take LDLC,and promoted the transformation of FC into CE.Ezetimibe up-regulated the expressions of SREBP-2 and LDLR in HepG2 cells,and increased the distribution of LDLR on the cell membrane.Conclusion Ezetimibe can promote the uptake of LDLC in liver cells by up-regulation of SREBP-2 and LDLR.关键词
依泽替米贝/甾醇调控元件结合蛋白2/低密度脂蛋白受体/低密度脂蛋白胆固醇Key words
Ezetimibe/Sterol regulatory element binding protein-2/Low density lipoprotein receptor/Low density lipoprotein cholesterol分类
医药卫生引用本文复制引用
方敏,李亚梅,向德标,龚勇珍,廖端芳,张彩平,郑熙隆..依泽替米贝通过上调甾醇调控元件结合蛋白2、低密度脂蛋白受体促进肝细胞摄取低密度脂蛋白胆固醇[J].中国动脉硬化杂志,2018,26(1):7-13,7.基金项目
国家自然科学基金项目(81600291、81773736) （81600291、81773736）
