利拉鲁肽对高糖条件下HepG2细胞胆固醇流出的影响  

Effects of liraglutide on cholesterol efflux in HepG2 cells under high glucose condition

作　　者：马春艳[1] 徐瑞霞[1] 李良[2] 吴亚茹 李建军[1] MA Chun-Yan;XU Rui-Xia;LI Liang;WU Ya-Ru;LI Jian-Jun(Division of Dyslipidemia;Department of Surgical Intensive Care Unit, State Key Laboratory of Cardiovascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences ＆ Peking Union Medical College, Beijing 100037, China)

机构地区：[1]中国医学科学院北京协和医学院国家心血管病中心阜外医院心血管疾病国家重点实验室血脂异常与心血管病诊治中心,北京市100037 [2]中国医学科学院北京协和医学院国家心血管病中心阜外医院心血管疾病国家重点实验室术后恢复中心,北京市100037

出　　处：《中国动脉硬化杂志》2018年第4期347-352,共6页Chinese Journal of Arteriosclerosis

基　　金：北京协和医学院协和青年基金(3332016018);首都卫生发展科研专项项目(2016-1-4035)

摘　　要：目的研究利拉鲁肽对高糖条件下HepG2细胞胆固醇流出的影响,检测相关蛋白表达并探讨其分子机制。方法体外培养HepG2细胞,以高糖刺激并以不同浓度利拉鲁肽干预,采用BODIPY-胆固醇荧光法检测利拉鲁肽对高糖条件下HepG2细胞胆固醇流出的影响,通过Western blot法分析三磷酸腺苷结合盒转运体A1（ABCA1）、ABCG1与清道夫受体B1蛋白表达及细胞外调节蛋白激酶1/2（ERK1/2）信号通路变化。结果利拉鲁肽可显著降低高糖（50 mmol/L）条件下HepG2细胞内荧光密度,增加ABCA1蛋白的表达,且增强ERK1/2的磷酸化水平。结论利拉鲁肽增强高糖条件下HepG2细胞中胆固醇流出,其机制可能与调控ERK1/2信号通路进而上调ABCA1表达有关。Aim To investigate the effects of liraglutide on cholesterol efflux in HepG2 cells under high glucose condition,and to detect the expression of related protein and further to explore its mechanism of action. Methods HepG2 cells were cultured in vitro,stimulating with high glucose and intervening with different concentrations of liraglutide.Effect of liraglutide on cholesterol efflux in HepG2 cells under high glucose condition was detected by using BODIPY-cholesterol fluorescence assay. Western blot was used to analyze the protein expressions of ATP-binding cassette transporter A1（ ABCA1）,ABCG1 and scavenger receptor B1 and the change of extracellular regulated protein kinase 1/2（ ERK1/2）signaling pathway. Results Liraglutide could significantly reduce the fluorescence density of HepG2 cells in high glucose（ 50 mmol/L） condition,increase the expression of ABCA1 protein and enhance the phosphorylation level of ERK1/2.Conclusion Liraglutide can promote cholesterol efflux in HepG2 cells under high glucose condition,and its mechanism may be related to the regulation of ERK1/2 signaling pathway and the up-regulation of ABCA1 expression.

关 键 词：利拉鲁肽 高糖 胆固醇流出 三磷酸腺苷结合盒转运体A1 信号通路 

分 类 号：R96[医药卫生—药理学]