络赛维对肝细胞脂肪变性的影响及机制  

Effect of rosavin on hepatocellular steatosis and its underlying mechanism

作　　者：王燊 蔡金慧 郑琳 张研 曾凯晴 徐启恩 冯燕敏 叶晓霞 WANG Shen;CAI Jin-hui;ZHENG Lin;ZHANG Yan;ZENG Kai-qing;XU Qi-en;FENG Yan-min;YE Xiao-xia(School of Pharmacy,Guangdong Medical University,Zhanjiang Guangdong 524023,China;The First Clinical College,Guangdong Medical University,Zhanjiang Guangdong 524023,China;School of Basic Medical Sciences,Guangdong Medical University,Zhanjiang Guangdong 524023,China)

机构地区：[1]广东医科大学药学院,广东湛江524023 [2]广东医科大学第一临床医学院,广东湛江524023 [3]广东医科大学基础医学院,广东湛江524023

出　　处：《中国药理学通报》2025年第3期466-474,共9页Chinese Pharmacological Bulletin

基　　金：广东省基础与应用基础研究基金项目(No 2018030310106);广东省大学生攀登计划项目(No pdjh2023b0236);广东省大学生创新创业训练计划项目(No S202310571061,S202410571044)。

摘　　要：目的探讨络赛维对肝细胞脂肪变性的影响及作用机制。方法采用游离脂肪酸(free fatty acid,FFA)作用AML^(-1)2和HepG2细胞诱导肝细胞脂肪变性,油红O染色和CCK-8实验确定FFA最佳诱导浓度。络赛维给药后CCK-8实验检测细胞活性,油红O染色观察肝细胞脂滴堆积情况,试剂盒检测甘油三酯(TG)、总胆固醇(TC)、谷草转氨酶(AST)、谷丙转氨酶(ALT)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、丙二醛(MDA)水平。网络药理学和分子对接分析络赛维影响非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD)的候选靶点,实时荧光定量PCR检测核心候选靶点在络赛维干预前后的表达。结果通过FFA诱导肝细胞脂肪变性,络赛维(25,50μmol·L^(-1))干预后以剂量依赖性形式降低肝细胞内脂滴数量,还可降低细胞TG、TC、AST、ALT水平,并升高SOD和GSH-Px水平、降低MDA水平。网络药理学分析和分子对接获得5个核心候选靶点:NOS3、MAPK14、PPARG、TNF-α、IGF-1,实时荧光定量PCR显示络赛维作用可明显降低FFA诱导后肝细胞内TNF-α、PPARG的基因表达。结论络赛维能够通过调控TNF-α和PPARG,降低肝细胞内的炎症反应、氧化应激水平和脂质积累,从而改善FFA诱导的肝细胞脂肪变性。Aim To investigate the effects of rosavin on hepatocellular steatosis and its mechanism of action.Methods AML^(-1)2 and HepG2 cells were induced to undergo hepatocellular steatosis by free fatty acids(FFA),and the optimal inducing concentration was determined by oil red O staining and CCK-8 assay.The cell activity was detected by CCK-8 assay after rosavin treatment,and the lipid droplet accumulation was observed by oil red O staining.The levels of triglyceride(TG),total cholesterol(TC),glutamic oxalacetic transaminase(AST),glutamic pyruvic transaminase(ALT),superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),and malondialdehyde(MDA)were detected by kits.The potential targets of rosavin in non-alcoholic fatty liver disease(NAFLD)were analyzedby network pharmacology and molecular docking,and the expression of core candidate targets before and after the rosavin intervention was detected by real-time fluorescence quantitative PCR.Results Hepatocyte steatosis was induced by FFA,and the intervention of rosavin(25,50μmol·L^(-1))reduced the number of intracellular lipid droplets in hepatocytes in a dose-dependent manner,also lowered the cellular levels of TG,TC,AST,ALT,elevated the levels of SOD and GSH-Px,and reduced the levels of MDA.Network pharmacological analysis and molecular docking yielded five core candidate targets:NOS3,MAPK14,PPARG,TNF-α,and IGF-1,and real-time fluorescence quantitative PCR showed that the action of loxavir significantly reduced the gene expression of TNF-αand PPARG in hepatocytes after FFA induction.Conclusions Rosavin can attenuate the inflammatory response,oxidative stress level,and lipid accumulation in hepatocytes by modulating TNF-αand PPARG,thereby ameliorating FFA-induced hepatocellular steatosis.

关 键 词：非酒精性脂肪性肝病 玫瑰红景天 络赛维 脂肪变性 TNFΑ PPARG 

分 类 号：R-332[医药卫生] R284.1R329.24R344.7R575.5