毛蕊异黄酮苷通过激活AMPK改善地塞米松诱导的HepG2细胞脂质合成  

Calycosin-7-O-β-D-glucoside reduces dexamethasone-induced lipid synthesis in HepG2 cells via AMPK activation

作　　者：许琬 朱琴 周非叶 邓儒元 Xu Wan;Zhu Qin;Zhou Feiye;Deng Ruyuan(Department of Gastroenterology and Hepatology,Shanghai Geriatric Medical Center,Shanghai 201104,China;Department of Gastroenterology and Hepatology,Zhongshan Hospital,Fudan University,Shanghai 200032,China;Department of Endocrinology and Metabolism,Renji Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200120,China)

机构地区：[1]上海市老年医学中心消化内科,201104 [2]复旦大学附属中山医院消化内科,上海200032 [3]上海交通大学医学院附属仁济医院内分泌科,200120

出　　处：《中华内分泌代谢杂志》2024年第4期333-338,共6页Chinese Journal of Endocrinology and Metabolism

基　　金：国家自然科学基金(81800684)。

摘　　要：目的探究毛蕊异黄酮苷(calycosin-7-O-β-D-glucoside,CG)改善糖皮质激素诱导肝细胞脂质合成的作用机制。方法地塞米松(dexamethasone,Dex)、CG、腺苷酸活化蛋白激酶(AMP-activated protein kinase,AMPK)激动剂AICAR、AMPK抑制剂compound C、AMPK失活(AMPK-DN)及组成性激活(AMPK-CA)腺病毒处理HepG2细胞后,使用CCK8法、油红O染色、三酰甘油和总胆固醇检测盒、实时定量PCR及Western印迹法分别检测细胞活性、细胞脂质含量、脂质合成相关基因的表达及AMPK的磷酸化水平。结果CG显著减少Dex诱导的HepG2细胞中脂质含量及脂质合成关键酶硬脂酰辅酶A去饱和酶(Scd1)、乙酰辅酶A羧化酶(ACC)、脂肪酸合成酶(Fasn)与转录因子固醇调控元件结合蛋白1c(Srebp-1c)的表达,并上调AMPK的磷酸化水平,而该保护效应可被AMPK抑制剂与AMPK-DN腺病毒所抑制。结论CG可通过激活AMPK抑制糖皮质激素诱导的肝细胞脂质合成。Objective To investigate the effect and underlying mechanism of calycosin-7-O-β-D-glucoside(CG)on glucocorticoid-induced lipid synthesis in hepatocytes.Methods After treating HepG2 cells with dexamethasone(Dex),CG,AMP-activated protein kinase(AMPK)agonist AICAR,AMPK inhibitor compound C,or adenovirus encoding dominant-negative mutant of AMPK(AMPK-DN)and constitutively active AMPK(AMPK-CA),the cell viability,lipid content,expression of lipogenesis-related genes and AMPK phosphorylation were detected using CCK8 assay,Oil red O staining,triglyceride and total cholesterol assay kits,real-time PCR,and Western blot,respectively.Results CG could significantly reduce the lipid content as well as expressions of key lipogenic enzymes including stearoyl-CoA desaturase 1(Scd1),acetyl-CoA carboxylase(ACC),fatty acid synthase(Fasn),and transcription factor sterol regulatory element-binding protein 1c(SREBP-1c)in dexamethasone-treated HepG2 cells.Furthermore,CG upregulated AMPK phosphorylation level.This protective effect was inhibited by AMPK inhibitor and AMPK-DN overexpression.Conclusion CG can reduce glucocorticoid-induced lipogenesis via AMPK activation.

关 键 词：毛蕊异黄酮苷 非酒精性脂肪性肝病 糖皮质激素 腺苷酸活化蛋白激酶 

分 类 号：R285[医药卫生—中药学]