基于网络药理学和实验验证的黄芪多糖拮抗TNF-α表达减轻小鼠代谢相关脂肪性肝病的作用机制研究  

A mechanistic study of astragalus polysaccharides in alleviating metabolic-associated fatty liver disease in mice through network pharmacology and experimental valida-tion to antagonize TNF-αexpression

作　　者：张格格 王晶[2] ZHANG Gege;WANG Jing(Graduate School of Baotou Medical College,Inner Mongolia University of Science and Technology,Baotou 014060;Department of Gastroenterology,the Second Affiliated Hospital of Baotou Medical College,Inner Mongolia University of Science and Technology,China)

机构地区：[1]内蒙古科技大学包头医学院研究生院,内蒙古包头014060 [2]内蒙古科技大学包头医学院第二附属医院消化科

出　　处：《胃肠病学和肝病学杂志》2025年第2期172-179,共8页Chinese Journal of Gastroenterology and Hepatology

基　　金：2022年度包头医学院创新团队发展计划项目(byjj-efytd-006)。

摘　　要：目的基于网络药理学方法推测黄芪多糖(astragalus polysaccharides,APS)治疗代谢相关脂肪性肝病(metabolic-associated fatty liver diseases,MAFLD)相关机制并开展动物实验进行验证。方法采用网络药理学方法找到APS的活性成分并利用数据库挖掘APS及MAFLD相关靶点并对以上靶点取交集,绘制交集靶点蛋白质相互作用网络图和核心靶点网络图。进行动物实验验证,将21只小鼠随机平均分为3组,分别为正常对照组、MAFLD模型组及MAFLD模型+APS干预组。MAFLD模型+APS干预组小鼠予以高脂饲料喂养8周,同时将APS以剂量为50 mg·kg^(-1)·d^(-1)对小鼠连续灌胃8周;MAFLD模型组及正常对照组小鼠分别以高脂饲料、标准维持饲料喂养8周,同时用等体积生理盐水对小鼠连续灌胃8周。给药结束后观察小鼠一般情况,计算肝指数,取小鼠肝脏组织进行HE染色,酶联免疫吸附实验测定小鼠血清及肝脏组织中TNF-α的含量,免疫组织化学方法分析小鼠肝脏组织中TNF-α的表达情况。结果通过网络药理学方法获得APS相关作用靶点292个,获得MAFLD相关作用靶点2254个,二者交集靶点104个。经过分析后筛选出22个APS治疗MAFLD的核心靶点,TNF为其中之一且节点大、颜色深,提示TNF是APS治疗MAFLD过程中重要的靶点之一。动物实验结果显示,与MAFLD模型组小鼠相比,APS的干预可以显著降低MAFLD小鼠的体质量、肝湿重及肝指数(P<0.01)。APS可以在组织病理学上改善MAFLD小鼠的肝脏组织。APS的干预还可以降低MAFLD小鼠血清及肝脏组织中TNF-α的浓度(P<0.05)。小鼠肝脏组织免疫组化实验结果显示,APS干预组小鼠阳性表达区域面积显著低于MAFLD模型组(P<0.001)。结论基于网络药理学及动物实验结果可知TNF是APS治疗MAFLD的重要靶点之一,APS可以通过拮抗TNF-α表达来减轻小鼠MAFLD。Objective To speculate on the mechanisms of astragalus polysaccharides(APS)in treating metabolicassociated fatty liver diseases(MAFLD),and conducting animal experiments for validation by using network pharmacology methods.Methods Using network pharmacology methods to identify the active components of APS and utilizing databases to explore the correlated target proteins of APS and MAFLD,and obtaining the intersection of the above targets,drawing the protein-protein interaction network diagram for intersecting targets and the core target network diagram.Animal experiments for validation,the 21 mice were randomly and evenly divided into three groups:normal control group,MAFLD model group and MAFLD model+APS intervention group.The mice in the MAFLD model+APS intervention group were fed a high-fat diet for 8 weeks,while concurrently administrating APS at a dosage of 50 mg·kg^(-1)·d^(-1)through continuous gavage for the same duration;the mice in the MAFLD model group and the normal control group were respectively fed with a high-fat diet and standard maintenance diet for 8 weeks,at the same time,mice were subjected to continuous gavage with an equivalent volume of saline for 8 weeks.After the administration concluded,the mice were observed for general condition,calculated the liver index,harvested mouse liver tissues for hematoxylin and eosin stai-ning,measured the levels of TNF-αin mouse serum and liver tissues by using enzyme-linked immunosorbent assay,con-ducted immunohistochemical analysis to assess the expression of TNF-αin mouse liver tissues.Results Through net-work pharmacology,292 potential target proteins were identified for APS,and 2254 target proteins were identified for MAFLD,104 common target proteins were obtained.After analysis,22 core target proteins for APS in treating MAFLD were selected.TNF was one of them,with a large node size and dark color,indicating its significance as one of the cru-cial targets in the process of APS treating MAFLD.The results of animal experiments showed that,compared to

关 键 词：黄芪多糖 代谢相关脂肪性肝病 TNF-Α 网络药理学 动物实验 

分 类 号：R575.5[医药卫生—消化系统]