基于网络药理学的饮久舒治疗非酒精性脂肪性肝病作用机制及实验验证  

Network pharmacological mechanism and experimental validation of Yinjiushu in the treatment of non-alcoholic fatty liver disease based on the homology of medicine and food

作　　者：王伟[1,2] 李毓秋[1] 劳慧敏 王凯 Wang Wei;Li Yuqiu;Lao Huimin;Wang Kai(Clinical Medical College of Shandong University,Jinan 250012,China;Department of Gastroenterology,Affiliated Hospital of Shandong University of Traditional Chinese Medicine,Jinan 250014,China;Department of Hepatology,Qilu Hospital of Shandong University,Jinan 250012,China)

机构地区：[1]山东大学临床医学院,济南250012 [2]山东中医药大学附属医院消化内二科,济南250014 [3]山东大学齐鲁医院肝病科,济南250012

出　　处：《国际中医中药杂志》2023年第8期989-996,共8页International Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金项目(81904128);山东省中医药科技发展计划项目(2019-0159);山东省博士后创新计划项目(202003069)。

摘　　要：目的基于药食同源理论,通过网络药理学探讨饮久舒治疗非酒精性脂肪性肝病(NAFLD)的分子机制,并进行实验验证。方法通过TCMSP筛选饮久舒药物活性成分和靶点。利用Cytoscape 3.7.2构建饮久舒“中药-成分-靶点”网络。利用TTD、GeneCards、DisGeNET等数据库获取NAFLD的潜在靶点,利用Venn图进行靶点映射获取饮久舒与NAFLD的交集靶点。在STRING数据库获取交集靶点的高置信度交互作用关系,筛选饮久舒治疗NAFLD的核心靶点。利用DAVID数据库对交集靶点进行GO功能富集分析及KEGG通路富集分析。通过动物实验进行验证,将48只大鼠按随机数字表法分为空白组、模型组、西药组及饮久舒高、中、低剂量组,每组8只。除空白组外,其余各组大鼠以高脂饲料喂养制备NAFLD模型,各组给予相应药物进行干预,定期称量大鼠体重,采用ELISA法检测大鼠血清GPT、GOT、TC、TG、IL-6、TNF-α、髓过氧化物酶(MPO)水平,计算肝指数,采用HE染色观察肝细胞脂肪变性程度,采用Western blot法检测CAT、NOS3、SOD、PI3K、p-Akt、Akt蛋白表达。结果获得NAFLD相关靶点8418个,饮久舒组方药物活性成分118个,作用于NAFLD的靶点共137个,核心靶点包括IL-6、TNF、VEGFA、TP53、JUN、CAT、NOS3、SOD等。KEGG通路富集通路筛选出20条相关信号通路,其中PI3K/Akt通路、钙离子通路、cAMP通路、TNF通路可能在治疗NAFLD中发挥关键作用。饮久舒与NAFLD的炎症反应、氧化应激、血管生成、自噬及细胞增殖、分化、代谢、凋亡等密切相关,或可通过促进细胞凋亡、抑制细胞增殖及迁移等方面治疗NAFLD。动物实验结果显示,饮久舒可降低NAFLD大鼠体重、肝湿重、肝指数,降低血清GPT、GOT、TG、TC及IL-6、TNF-α、MPO水平,上调肝组织CAT、NOS3、SOD表达,并激活PI3K/Akt通路关键蛋白。结论饮久舒可通过抑制炎症介质释放,改善肝细胞脂代谢紊乱,修复氧化应激损伤,促�Objective To the molecular mechanism of Yinjiushu in the treatment of non-alcoholic fatty liver disease(NAFLD)by network pharmacology based on the theory of homology of medicine and food;To conduct experimental verification.Methods The active components and targets of the Yinjiushu were screened through the TCMSP platform.Cytoscape 3.7.2 was used to construct the"Chinese materia medica-component-target"network of Yinjiushu.The potential targets of NAFLD were obtained by using TTD,GeneCards database and DisGeNET database,and the intersection targets of Yinjiushu and NAFLD were obtained by mapping targets with Venn diagram.The high confidence interaction relationship of intersection targets was obtained in STRING database,and the core targets of Yinjiushu in treating NAFLD were screened out.GO function and KEGG pathway enrichment of common targets were analyzed by David database,and the above results were further verified by animal experiments.The rats were divided into blank group,model group,Western medicine group and Yinjiushu high-,medium-and low-dosage groups according to random number table method,with 8 rats in each group.Except the blank group,rats in other groups were fed with high-fat diet to prepare NAFLD model.Each group was given corresponding drugs for intervention.The rats were weighed regularly.The serum contents of GPT,GOT,TC,TG,IL-6,TNF-α,MPO of rats were detected by ELISA.The liver index was calculated.The degree of fatty degeneration of hepatocytes was observed by HE.The expressions of CAT,NOS3,SOD,PI3K,p-Akt,Akt protein were detected by Western blot.Results A total of 8418 NAFLD-related targets,118 kinds of active components from Yinjiushu,and 137 targets acting on NAFLD were screened.The core targets included IL-6,TNF,VEGFA,TP53,JUN,CAT,NOS3,SOD,etc.20 related signaling pathways were screened from KEGG enrichment pathway,among which PI3K/Akt pathway,calcium ion pathway,cAMP pathway and TNF pathway may play key roles in the treatment.Yinjiushu was closely related to inflammatory reaction,oxida

关 键 词：非酒精性脂肪肝 饮久舒 药食同源 网络药理学 作用机制 实验验证 

分 类 号：R285[医药卫生—中药学]