人参皂苷Rg1激活腺苷酸激活蛋白激酶抑制体外诱导的非酒精性脂肪性肝细胞模型脂质沉积  

Ginsenoside Rg1 activates AMPK to inhibit lipid deposition in a cell model of non-alcoholic fatty liver disease

作　　者：肖晴 黄文祥[1] 章述军[1] 阳成[1] 李佳俊[1] 赵金秋[1] 高月 XIAO Qing;HUANG Wenxiang;ZHANG Shujun;YANG Cheng;LI Jiajun;ZHAO Jinqiu;GAO Yue(Departmentof Infectious Diseases,the First Affiliated Hospital of Chongqing Medical University,Chongqing,400016,China)

机构地区：[1]重庆医科大学附属第一医院感染科

出　　处：《第三军医大学学报》2019年第14期1343-1349,共7页Journal of Third Military Medical University

基　　金：重庆市科委基础科学与前沿技术研究重点项目(CSTC2015jcyjBX0079)~~

摘　　要：目的探讨人参皂苷Rg1对非酒精性脂肪性肝细胞模型脂质沉积的作用及其分子机制。方法用0.25 mmol/L棕榈酸处理HepG2细胞24 h构建非酒精性脂肪肝细胞模型;加或不加10μmol/L AMPK抑制剂(Compound C,CC)预处理1 h,再使用40μg/mL人参皂苷Rg1或5μmol/L二甲双胍处理6 h。微量法检测细胞内甘油三酯(triglyceride, TG)含量;油红O染色观察脂滴聚集情况。RT-qPCR及Western blot检测腺苷酸激活蛋白激酶(AMP-activated protein kinase,AMPK)通路相关基因及蛋白的变化。结果与对照组比较,模型组细胞内TG、油红O染色吸光度增加(P<0.05)。Rg1能减少TG及油红O染色吸光度(P<0.05)。Rg1能增加被棕榈酸抑制的腺苷酸激活蛋白激酶(AMPK)和乙酰辅酶A羧化酶(acetyl-CoA carboxylase,ACC)的磷酸化,下调胆固醇结合调节元件蛋白(sterol regulatory element binding proteins-1c,SREBP-1C)和脂肪酸合成酶(fatty acid synthase,FAS)的表达(P<0.05),CC预处理能显著逆转Rg1的改善作用及其对AMPK通路的影响(P<0.05)。结论 Rg1可通过调控腺苷酸激活蛋白激酶通路减少非酒精性脂肪性肝病细胞模型脂质沉积。Objective To investigate the effect of ginsenoside Rg1 on lipid deposition in a cell model of non-alcoholic fatty liver disease(NAFLD) and explore the molecular mechanism. Methods HepG2 cells were treated with 0.25 mmol/L palmitic acid for 24 h to induce changes mimicking NAFLD, followed by treatment with 40 μg/mL ginsenoside Rg1 or 5 μmol/L metformin for 6 h with or without pretreatment with 10 μmol/L Compound C(CC, an AMPK inhibitor) for 1 h. The level of triglyceride(TG) in the cells was detected using a micromethod, and the accumulation of lipid droplets was observed using Oil Red O staining. RT-qPCR and Western blotting were employed to detect the alterations in the mRNA and protein expression of the key genes related to the AMPK pathway. Results Compared with the control cells, the cell model of NAFLD showed significantly increased intracellular TG level and lipid droplet accumulation(P<0.05), which were both reduced obviously after Rg1 treatment(P<0.05). Rg1 significantly abolished palmitic acid-induced inhibition of phosphorylation of intracellular AMPK and acetyl-CoA carboxylase(ACC), and down-regulated the expression of sterol regulatory element-binding protein-1 c and fatty acid synthase(P<0.05). Pretreatment with CC significantly antagonized the effects of Rg1 on intracellular TG, lipid deposition and AMPK pathway in palmitic acid-induced cells(P<0.05). Conclusion Ginsenoside Rg1 can ameliorate lipid deposition in the cell model of NAFLD by activating the AMPK pathway.

关 键 词：非酒精性脂肪性肝病 人参皂苷RG1 脂质沉积 腺苷酸活化蛋白激酶 

分 类 号：R282.71[医药卫生—中药学] R285.5[医药卫生—中医学]