刺甘草查尔酮下调ASK1-JNK信号通路抗FFA诱导的非酒精性脂肪性肝病  

Echinatin down-regulates ASK1-JNK signaling pathway against FFA induced non-alcoholic fatty liver disease

作　　者：何倞婧 黄欣 张波 王晓琴[2] HE Jing-jing;HUANG Xin;ZHANG Bo;WANG Xiao-qin(School of Pharmacy,Shihezi University,Shihezi Xinjiang 832002,China;School of Pharmacy,Chengdu University,Sichuan Institute of Antibiotic Industry,Chengdu 610106,China)

机构地区：[1]石河子大学药学院,新疆植物药资源利用教育部重点实验室,新疆石河子832002 [2]成都大学药学院,四川省抗菌素工业研究所,四川成都610106

出　　处：《中国药理学通报》2023年第5期882-889,共8页Chinese Pharmacological Bulletin

基　　金：新疆生产建设兵团重大科技项目(No 2020AA005);新疆兵团科技创新领域中青年领军人才项目(NO.2018CB019)。

摘　　要：目的探究刺甘草查尔酮(echinatin,Ech)对游离脂肪酸(free fatty acids,FFA)诱导人肝癌(HepG2)细胞的非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)模型的影响及作用机制。方法实验分组为对照组、FFA模型组、Ech组(0.3、1、3μmol·L^(-1));通过细胞形态学和化学荧光法分析细胞内脂质积累、线粒体损伤、氧化应激以及凋亡情况;分子对接预测Ech与ASK1和JNK蛋白的亲和力;Western blot分析NF-κB p65、BAX以及ASK1-JNK信号通路相关蛋白表达情况。结果相较于FFA模型组,Ech组细胞脂质积累明显减轻,线粒体损伤以及氧化应激情况得到改善,凋亡率明显下降,并且NF-κB p65、BAX、p-ASK1、JNK、p-JNK的蛋白表达量均明显降低。结论Ech改善FFA诱导的HepG2细胞脂质积累、线粒体功能障碍、氧化应激、细胞凋亡以及炎症反应,可能与下调ASK1-JNK信号通路有关。Aim To investigate the effect of echinatin on the non-alcoholic fatty liver disease model of free fatty acids(FFA)-induced HepG2 cells and its mechanism.Methods The experimental groups were divided into control group,FFA model group and echinatin group(0.3,1,3μmol·L^(-1));intracellular lipid accumulation,mitochondrial damage,oxidative stress and apoptosis were analyzed by cell morphology and chemical fluorescence methods;molecular docking was used to predict the affinity of Ech to ASK1 and JNK proteins;Western blot was used to analyze the expressions of NF-κB p65,BAX and ASK1-JNK signaling pathway-related proteins.Results Compared with the FFA model group,the lipid accumulation of cells in the echinatin group was significantly reduced,the mitochondrial damage and oxidative stress were improved,the apoptosis rate significantly decreased,and the levels of NF-κB p65,BAX,p-ASK1,JNK,and p-JNK were significantly reduced.The protein expression levels were significantly reduced.Conclusion Echinatin improves FFA-induced lipid accumulation,mitochondrial dysfunction,oxidative stress,apoptosis and inflammatory response in HepG2 cells,which is highly related to the inhibition of ASK1-JNK signaling pathway.

关 键 词：非酒精性脂肪性肝病 游离脂肪酸 HEPG2细胞 刺甘草查尔酮 凋亡 ASK1-JNK信号通路 脂质积累 氧化应激 

分 类 号：R284.1[医药卫生—中药学] R329.24[医药卫生—中医学] R329.25R344R349.1