糖脂代谢异常对丙型肝炎病毒感染肝细胞SIRT1-AMPK信号通路的影响  

The effect of glucose and lipid metabolism disorders on silent information regulator 1 and AMP-activated protein kinase signaling pathway in HCV infected hepatocytes

作　　者：于建武[1] 李明荣[1] 张晓宇[1] 孙丽杰[1] 赵勇华[1] 刘伟[2] YU Jian-wu;Li Ming-rong;ZHANG Xiao-yu;SUN Li-jie;ZHAO Yong-hua;LIU Wei(Department of Infectious Diseases, The Second Affiliated Hospital, Harbin Medical University, Harbin 150086, China)

机构地区：[1]哈尔滨医科大学附属第二医院感染病科,150086 [2]哈尔滨医科大学附属第二医院科研实验中心,150086

出　　处：《肝脏》2019年第1期28-30,共3页Chinese Hepatology

基　　金：黑龙江省教育厅科学技术研究项目(12541266)

摘　　要：目的探讨不同浓度的葡萄糖、油酸对丙型肝炎病毒(HCV)感染肝细胞沉默信息调节因子1(SIRT1)-AMP激活蛋白激酶(AMPK)信号通路的影响。方法表达HCV核心蛋白的质粒转染HepG2细胞。表达HCV核心蛋白的HepG2细胞在不同终浓度的葡萄糖或油酸的无血清DMEM培养液中孵育24h。分别应用液体闪烁计数仪和蛋白质印迹检测SIRT1和AMPK活性及蛋白的表达。结果随着葡萄糖浓度(1、2、4.5g/L)不断升高,SIRT1活性(1.0±0.2、0.6±0.15、0.2±0.05)及SIRT1蛋白表达(0.9±0.2、0.4±0.1、0.1±0.05)下降,AMPK活性(1.0±0.2、0.5±0.08、0.22±0.05)及p-AMPK蛋白表达(0.9±0.2、0.4±0.1、0.2±0.05)下降;随着油酸浓度(0、300、500uM/L)不断升高,SIRT1活性(1.0±0.2、0.6±0.1、0.2±0.05)及SIRT1蛋白表达(0.9±0.2、0.5±0.1、0.2±0.05)下降,AMPK活性(1.0±0.2、0.5±0.1、0.1±0.05)及p-AMPK蛋白表达(0.9±0.2、0.5±0.1、0.2±0.05)下降。结论高糖、高油酸可下调HCV感染肝细胞SIRT1-AMPK信号通路的活性及表达。Objective The aim of this study was to investigate the effect of different concentrations of glucose or oleic acid on expression and activity of silent information regulator 1 (SIRT1) and adenosine monophosphate-activated protein kinase (AMPK) in hepatitis C virus (HCV) infected hepatocytes. Methods Plasmid expressing HCV core protein was transfected into HepG2 cells, which were incubated for 24 hours in serum-free DMEM medium with different final concentrations of glucose or oleic acid. The activity and expression of SIRT1 and AMPK were detected using scintillation counting and western blot, respectively. Results With increasing glucose concentration(1 g/L, 2 g/L, 4.5 g/L), SIRT1 activity (1.0±0.2, 0.6±0.15, 0.2±0.05) and expression (0.9±0.2, 0.4±0.1, 0.1±0.05) were decreased, AMPK activity (1.0±0.2, 0.5±0.08, 0.22±0.05) and expression (0.9±0.2, 0.4±0.1, 0.2±0.05) were decreased. With the increase of oleic acid concentration(0, 300 μM/L, 500 μM/L), SIRT1 activity (1.0±0.2, 0.6±0.1, 0.2±0.05) and expression (0.9±0.2, 0.5±0.1, 0.2±0.05) were decreased, AMPK activity (1.0±0.2, 0.5±0.1, 0.1±0.05) and expression of p-AMPK (0.9±0.2, 0.5±0.1, 0.2±0.05) were decreased. Conclusion High glucose and high oleic acid may down-regulate the activity and expression of SIRT1-AMPK signaling pathway in HCV infected hepatocytes.

关 键 词：丙型肝炎病毒 高糖 高油酸 沉默信息调节因子1 SIRT1 AMP激活蛋白激酶 AMPK 

分 类 号：R512.63[医药卫生—内科学]