基于网络药理学探讨参苓白术散改善儿童肥胖脂肪组织炎症的分子机制及动物实验验证  

Exploration on the Molecular Mechanism of Shenling Baizhu Powder in Improving Adipose Tissue Inflammation in Children with Obesity Based on Network Pharmacology and Animal Experimental Verification

作　　者：牛昶淼 梁莉婷 殷永凯 燕小宁 张凯茜 牛耕田 NIU Changmiao;LIANG Liting;YIN Yongkai;YAN Xiaoning;ZHANG Kaixi;NIU Gengtian(The First Clinical College of Shanxi University of Chinese Medicine,Jinzhong 030619,China;The Third Clinical College of Shanxi University of Chinese Medicine,Jinzhong 030619,China;Wanrong County Medical Group Jiedian Town Health Center,Yuncheng 044000,China)

机构地区：[1]山西中医药大学第一临床学院,山西晋中030619 [2]山西中医药大学第三临床学院,山西晋中030619 [3]万荣县医疗集团解店镇卫生院,山西运城044000

出　　处：《中国中医药信息杂志》2024年第12期27-34,共8页Chinese Journal of Information on Traditional Chinese Medicine

基　　金：山西省基础研究计划自然科学研究面上项目(202103021224296);山西省中医药管理局科研项目(2022ZYYC100);山西中医药大学科技创新能力培育计划项目(2023PY-TH-06);山西中医药大学附属中西医结合医院硕导基金科技兴医创新计划(2022-S-18)。

摘　　要：目的借助网络药理学和分子对接方法,挖掘参苓白术散改善儿童肥胖脂肪组织炎症的有效成分及可能的作用靶点和机制,并通过动物实验进行初步验证。方法利用TCMSP数据库筛选参苓白术散活性成分和靶点,利用GeneCards、OMIM、DisGeNET数据库获取疾病靶点,药物与疾病的靶点取交集后构建活性成分-靶点网络,构建蛋白相互作用网络并获取核心靶点,进行GO和KEGG通路富集分析,对关键成分与核心靶点进行分子对接。构建高脂饮食诱导的幼龄肥胖大鼠模型,予参苓白术散灌胃,检测大鼠血清三酰甘油、总胆固醇及附睾脂肪组织肿瘤坏死因子-α、白细胞介素-1β、γ干扰素、Fas mRNA表达。结果参苓白术散改善儿童肥胖微炎症的关键成分为荜茇明宁碱、金合欢素、木犀草素、海风藤酮、亚麻油酸乙酯、高丽槐素等,药物-疾病共同靶点515个,核心靶点为TP53、SRC、PIK3R1、HSP90AA1、PIK3CA。GO富集分析结果涉及炎症反应、MAPK级联正向调控、膜筏、丝氨酸/苏氨酸/酪氨酸蛋白激酶活性等,KEGG通路富集分析结果包含代谢、免疫、内分泌及癌症和相关肝病等信号通路。分子对接结果表明,关键成分与核心靶点具有良好的结合活性。动物实验结果表明,参苓白术散具有改善模型大鼠炎症指标及代谢指标的作用。结论参苓白术散能够通过多种活性成分调控多个靶点,影响多条信号通路,通过特定的生物学过程及相关通路调节炎性反应、调节免疫过程、改善胰岛素抵抗、调节糖脂代谢等,共同发挥改善儿童肥胖脂肪组织炎症的作用。Objective To explore the effective components and possible targets and mechanism of Shenling Baizhu Powder in improving adipose tissue inflammation in children with obesity with the help of network pharmacology and molecular docking method;To conduct preliminary verification through animal experiments.Methods The active components and targets of Shenling Baizhu Powder were screened through the TCMSP database.GeneCards,OMIM,DisGeNET databases were used to obtain the disease targets.An active component-target network was constructed by taking the intersection of drug and disease targets.Protein-protein interaction networks were constructed and core targets were obtained for GO and KEGG pathway enrichment analysis.Molecular docking validation was performed to key components and core targets.Animal experiments were conducted by establishing a model of young obese rats induced by high fat diet,and Shenling Baizhu Powder were given for gavage.The contents of TG and TC in serum and mRNA expressions of TNF-α,IL-1β,INF-γand Fas in rat adipose tissue of epididymis were detected.Results The key components of Shenling Baizhu Powder to improve the microinflammation of obesity in children were piperlonguminine,acacetin,luteolin,denudatin B,mandenol,inermine,etc.There were 515 common drug-disease targets,and the core targets were TP53,SRC,PIK3R1,HSP90AA1 and PIK3CA.The results of GO enrichment analysis included inflammatory response,positive regulation of MAPK cascade,membrane raft,protein serine/threonine/tyrosine kinase activity,etc.KEGG pathway enrichment analysis results included metabolic,immune,endocrine,cancer and related liver disease signaling pathways.The results of molecular docking showed that the key components could play a regulatory role on the core target.Animal experiments showed that Shenling Baizhu Powder could improve microinflammation and metabolic indexes of model rats.Conclusion Shenling Baizhu Powder can act on multiple targets through various active components and multiple signaling pathways,adjustin

关 键 词：参苓白术散 网络药理学 儿童肥胖 炎症 代谢紊乱 实验验证 

分 类 号：R285[医药卫生—中药学]