网络药理学结合分子对接研究地格达-8味散治疗胆汁淤积型肝炎的作用机制  

Study on the mechanism of Digeda-8 powder on cholestatic hepatitis by Network pharmacology combined with molecular docking

作　　者：宝乌日力嘎 包明兰[1,2] 拉喜那木吉拉 侯亚星 娜仁呼 塔那 BAO Wuriliga;BAO Minglan;Laxinamujila;HOU Yaxing;Narenhu;Tana(Inner Mongolia Minzu University,Tongliao,Inner Mongolia,028000 P.R.China;Key Laboratory of Mongolian Medicine Research and Development Engineering,Ministry of Education,Inner Mongolia Minzu University,Tongliao,Inner Mongolia,028000 P.R.China)

机构地区：[1]内蒙古民族大学,内蒙古通辽028000 [2]内蒙古民族大学蒙医药研发工程教育部重点实验室,内蒙古通辽028000

出　　处：《华西药学杂志》2025年第1期35-40,共6页West China Journal of Pharmaceutical Sciences

基　　金：2023年度自治区直属高效基本科研业务费-杰青优青培育项目(GXKY23Z048);内蒙古自治区教育厅一流学科科研专项项目(YLXKZX-NMD-002);内蒙古民族大学蒙药炮制研究科研创新团队项目(mdpz20220110)。

摘　　要：目的 结合网络药理学和分子对接技术研究地格达-8味散治疗α-萘异硫氰酸酯(ANIT)诱导大鼠胆汁淤积型肝炎模型的机制。方法 建立ANIT致大鼠胆汁淤积型肝炎模型,观察地格达-8味散对大鼠胆汁淤积型肝炎的影响;利用Cytoscape软件建立“疾病-药物-靶点”网络,确定生物学过程和信号通路;结合生物信息学方法,对其中的活性物质和作用靶标进行分子对接,初步验证其作用机制。结果 地格达-8味散可治疗大鼠ANIT致胆汁淤积型肝炎,并改善肝脏病理损伤。网络药理学预测地格达-8味散主要成分对应565个靶基因,胆汁淤积型肝炎相关基因885个,二者共有靶点131个;其中,STAT3、TNF、TP53、AKT1、SRC、VEGFA、IL1B、CASP3、PIK3R1、MAPK8等为关键蛋白。地格达-8味散的主要化学成分能与预测的靶点良好对接。结论 地格达-8味散通过AGE-RAGE信号通路、脂质与动脉粥样硬化、流体切应力和动脉粥样硬化、肿瘤坏死因子等信号通路发挥作用,且可能通过调控TNF、AKT1、TP53、SRC、STAT3蛋白起到防治胆汁淤积型肝炎的作用。OBJECTIVE To study the therapeutic mechanism of Digeda-8 powder on the α-naphthyl isothiocyanate(ANIT)-induced rat model of cholestatic hepatitis by Network pharmacology combined with molecular docking.METHODS A model of ANIT-induced cholestatic hepatitis in rats were established, and the effects of Digeda-8 powder on cholestatic hepatitis in rats were observed.Cytoscape software was used to establish a disease-drug-target interaction network to identify biological processes and signaling pathways.On this basis, combined with bioinformatics methods, molecular docking of active substances and targets was carried out to preliminarily explore the mechanism of action.RESULTS Digeda-8 powder could treat ANIT-induced cholestatic hepatitis and improve liver pathological damage in rats.Network pharmacology predicted that there were 565 target genes corresponding to the main components of Digeda-8 powder, 885 genes related to cholestatic hepatitis, and 131 targets shared by drugs and cholestatic hepatitis.Among them, STAT3,TNF,TP53,AKT1,SRC,VEGFA,IL1B,CASP3,PIK3R1,MAPK8 and other core targets were identified as key proteins.The main chemical components of Digeda-8 powder exhibited strong clocking affinities with the predited targets.CONCLUSION Digeda-8 powder may play a role in the prevention and treatment of cholestatic hepatitis through AGE-RAGE signaling pathway, lipid and atherosclerosis, fluid shear stress and atherosclerosis, tumor necrosis factor and other signaling pathways, and may play a role in the prevention and treatment of cholestatic hepatitis through the regulation of TNF,AKT1,TP53,SRC,and STAT3 proteins.

关 键 词：地格达-8味散 胆汁淤积型肝炎 网络药理学 分子对接 炎症 生物信息学 

分 类 号：R96[医药卫生—药理学]