摘要
目的:探讨大黄素改善油酸+棕榈酸诱导非酒精性脂肪肝(nonalcoholic fatty liver disease,NAFLD)脂质堆积模型的机制。方法:利用网络药理学预测大黄素干预NAFLD的信号通路;在体外利用油酸+棕榈酸模拟NAFLD的体外模型,15、30μM大黄素干预NAFLD体外模型48 h,检测细胞内甘油三酯(triglycerides,TG)含量,油红染色评价细胞脂质堆积情况,蛋白质免疫印迹(western blot,WB)检测总磷脂酰肌醇3-激酶(Phosphatidylinositol 3-kinase,PI3K)、蛋白激酶Bβ(RAC-beta serine/threonine-protein kinase,AKT2)、磷酸化叉头框蛋白1(Phospho-forkhead box,pFoxo1)/叉头框蛋白1(forkhead box,Foxo1)及核pFoxo1/Foxo1,实时荧光定量PCR检测PI3K、AKT2、Foxo1、微粒体甘油三酯转运蛋白、载脂蛋白CⅢ(Apolipoprotein,apoC-Ⅲ)的表达。结果:网络药理学预测大黄素共得到34个靶点,这些靶点显著富集在胰岛素抵抗、PI3K/AKT/Foxo1信号通路中。15、30μM大黄素干预的细胞内TG含量减少;大黄素能改善油酸+棕榈酸诱导BRL细胞的脂质堆积;30μM大黄素可显著上调模型组总PI3K、AKT,下调pFoxo1/Foxo1;30μM大黄素组可下调模型组MTTP、apoC-Ⅲ的表达。结论:大黄素可能通过调节PI3K/AKT/Foxo1降低脂质的堆积。
Objective:To investigate the mechanism of emodin in improving lipid accumulation model with NAFLD induced by oleic acid+palmic acid.Methods:Network pharmacology was utilized to predict emodin in the intervention of the signaling pathway of NAFLD;the in-vitro models of NAFLD were simulated using oleic acid+palmic acid,and intervened with 15 and 30μM of emodin for 48 hours,to detect the contents of TG,oil red O(ORO)staining was used to assess cell lipid accumulation,WB was applied to measure PI3K,AKT2,pFoxo1/Foxo1 and nuclear pFoxo1/Foxo1,real-time quantitative PCR was utilized to detect the expressions of PI3K,AKT2,Foxo1,microsomal triglyceride transfer protein and apoC-Ⅲ.Results:In total,34 targets were predicted for emodin by network pharmacology,and these targets were significantly enriched in the signaling pathways such as insulin resistance and PI3K/AKT/Foxol.The contents of TG were lowered in the cells after intervened with 15 and 30μM of emodin;emodin could improve lipid accumulation in BRL cells induced by oleic acid+palmic acid;30μM of emodin could noticeably upregulate the levels of PI3K and AKT of the model group,and downregulate pFoxo1/Foxo1;30μM of emodin could lower the expressions of MTTP and apoC-Ⅲof the model group.Conclusion:Emodin could reduce lipid accumulation possibly through adjusting PI3K/AKT/Foxol.
作者
吴海滨
林基伟
宋晓容
程波敏
刘卓超
朱艳萍
谭梅傲
WU Haibin;LIN Jiwei;SONG Xiaorong;CHENG Bomin;LIU Zhuochao;ZHU Yanping;TAN Meiao(Preventive Medicine Center,Shenzhen Hospital of TCM,Shenzhen 518033,China;Chongqing Hospital of TCM,Chongqing 404121,China)
出处
《西部中医药》
2025年第7期18-23,共6页
Western Journal of Traditional Chinese Medicine
基金
国家自然科学青年基金(82204953)
广东省中医药局科研项目(20211325)
深圳市卫生健康委员会医防融合中医药组项目(深卫健体改〔2019〕25号)
深圳市中医“治未病”重点专科建设项目
成都中医药大学杏林学者科研提升计划(YYZX2021056)
重庆市自然科学基金—博士后项目(CSTB2022NSCQ-BHX0032)。
