茵陈公英汤通过IRS/AKT/FoxO1和TLR4/NF-κB信号通路改善非酒精性脂肪肝病  

Yinchen Gongying Decoction(茵陈公英汤)Ameliorates NAFLD via IRS/AKT/FoxO1 and TLR4/NF-κB Signaling Pathways

作　　者：宋汶轩 李爽 安梦娇 李佳琪 郭纪元 蒋声赫 李沙 储金秀 安春娜 郝思钰 韩小蕾 胡宝丰 齐亚娟 SONG Wenxuan;LI Shuang;AN Mengjiao;LI Jiaqi;GUO Jiyuan;JIANG Shenghe;LI Sha;CHU Jinxiu;AN Chun;HAO Siyu;HAN Xiaolei;HU Baofeng;QI Yajuan(School of Basic Medical Sciences,North China University of Science and Technology,Tangshan 063210;Qian'an Hospital of Chinese Medieine,Tangshan 063210;School of Pharmacy,North China University of Science and Technology,Tangshan 063210;Key Laboratory of Basic Research on New Drugs,Tangshan 063210;Hebei Key Laboratory of Basic Medical Sciences for Chronie Diseases,Tangshan 063210)

机构地区：[1]华北理工大学基础医学院,唐山063210 [2]迁安中医医院,唐山063210 [3]华北理工大学药学院,唐山063210 [4]唐山市新药基础研究重点实验室,唐山063210 [5]河北省慢性疾病基础医学重点实验室,唐山063210

出　　处：《中药药理与临床》2025年第2期8-15,共8页Pharmacology and Clinics of Chinese Materia Medica

基　　金：河北省中医药联合基金重点项目(编号:H2022209087);河北省自然科学基金项目(编号:H2021209013);国家自然科学基金项目(编号:81471022);河北省高等学校科学技术研究项目(编号:ZD2022141)。

摘　　要：目的:基于网络药理学探讨茵陈公英汤对非酒精性脂肪肝病(NAFLD)的改善作用及机制。方法:通过网络药理学分析茵陈公英汤与NAFLD的差异基因,进行基因GO富集分析与KEGG通路富集分析;使用Cytoscape软件构建“茵陈公英汤入血成分-靶点-通路”分析,从而预测茵陈公英汤对NAFLD的作用机制;给予60%高脂饲料构建小鼠NAFLD模型,随机分为正常对照组、模型对照组、盐酸吡格列酮0.002 g/kg组和茵陈公英汤1.5、3、6 g/kg组,药物干预6 w,称小鼠体质量、肝质量;于试验结束后检测天冬氨酸氨基转移酶(AST)和丙氨酸氨基转移酶(ALT)活力,血清甘油三脂(TG)和血糖含量;HE染色观察肝脏病理情况,油红O染色观察肝脏脂质沉积;实时定量PCR法检测肝脏糖脂代谢和炎症因子的基因表达;Western blot法检测肝脏胰岛素和炎症信号通路蛋白的表达。结果:网络药理学分析表明茵陈公英汤治疗NAFLD的潜在治疗靶点共224个,其核心靶点包括AKT、FoxO、TLR4、NF-κB等,富集分析显示这些靶点可能通过胰岛素抵抗、FoxO、脂代谢、炎症、AKT等信号通路改善NAFLD;经NAFLD模型小鼠验证发现,与模型对照组比较,茵陈公英汤各组小鼠的体质量降低,肝脏脂质沉积减轻,肝功能改善,血清TG降低,糖代谢异常改善(P<0.05或P<0.01);肝脏Glut4 mRNA表达上调,G6pase、Pepck、Acc、Scd1、Fasn、Il1β、Il6、Il8和Il11 mRNA表达下调;肝脏IRS1、IRS2、p-AKT/AKT和Glut4蛋白表达上调,FoxO1、TLR4、p-NF-κB/NF-κB、IL-1β、IL-6和IL-17A的蛋白表达下调。结论:茵陈公英汤可改善NAFLD,其机制涉及改善胰岛素的IRS1/IRS2/AKT/FoxO1通路和抑制炎症TLR4/NF-κB信号通路。Objective:To investigate the effect and mechanism of Yinchen Gongying Decoction(茵陈公英汤)in treating non-alcoholic fatty liver disease(NAFLD)based on network pharmacology.Methods:Network pharmacology was employed to predict the common genes shared by Yinchen Gongying Decoction and NAFLD,and gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrich-ment analyses were carried out for these genes.Cytoscape was used to establish the"absorbed components of Yinchen Gongying Decoction-target-pathway"network for revealing the mechanism of Yinchen Gongying Decoction in treating NAFLD.Subsequently,a mouse model of NAFLD was established with a 60%high-fat diet,and mice were randomized into normal,model,pioglitazone hydrochloride(0.002 g/kg),and Yinchen Gongying Decoction(1.5,3.0,and 6.0 g/kg)groups.The mice were then treated with corresponding agents for 6 successive weeks,during which the body weight and liver weight were measured.At the end of the experiment,liver function indicators including aspar-tate aminotransferase(AST)and alanine aminotransferase(ALT),serum triglyceride(TG)level,and blood glucose level were measured.Hematoxylin-eosin staining and Oil red O staining were adopted to assess the pathological changes in the liver tissue.Real-time quantitative PCR was employed to determine the mRNA levels of genes involved in sugar and lipid metabolism and inflammatory mediators in the liver tis-sue.Western blotting was employed to determine the expression levels of proteins in the insulin and inflammation signaling pathways.Results:A total of 224 targets were predicted to be involved in the treatment of NAFLD with Yinchen Gongying Decoction,among which the core targets included protein kinase B(AKT),foxhead box O(FoxO),Toll-like receptor 4(TLR4),and nuclear factor-kappa B(NF-κB).The enrichment analyses suggested that these targets were involved in insulin resistance,FoxO,lipid metabolism,inflammation,and AKT signa-ling pathways.The animal experiment showed that Yinchen Gongying Decoction r

关 键 词：茵陈公英汤 网络药理学 非酒精性脂肪性肝病 糖代谢 脂代谢 胰岛素抵抗 炎症 

分 类 号：R285.5[医药卫生—中药学]