基于网络药理学研究大建中汤治疗术后肠梗阻作用机制  

Mechanism of Dajianzhong Decoction(大建中汤)against Postoperative Ileus:Based on Network Pharmacology

作　　者：蒋淼[1] 吴纯洁[1] 王家葵[1] JIANG Miao;WU Chunjie;WANG Jiakui(School of Pharmacy,Chengdu University of Traditional Chinese Medicine,Key Laboratory of Standardization of Chinese Herbal Medicine,Ministry of Education,State Key Laboratory of Southwestern Chinese Medicine Resource,Chengdu 611137)

机构地区：[1]成都中医药大学药学院,中药标准化教育部重点实验室,西南特色中药资源国家重点实验室,成都611137

出　　处：《中药药理与临床》2023年第4期7-13,共7页Pharmacology and Clinics of Chinese Materia Medica

基　　金：四川省中医药管理局专项(编号:2020HJZX001);成都市知识产权专项(编号:202000092)。

摘　　要：目的:基于网络药理学筛选大建中汤中有效成分及作用靶点,并结合巨噬细胞炎症模型探讨其治疗术后肠梗阻(Postoperative ileus, POI)潜在作用机制。方法:使用TCMSP、TCMID数据库查找大建中汤中四味药成分,结合生物利用度以及类药性等条件挖掘其有效成分,通过疾病数据库挖掘术后肠梗阻相关基因,构建大建中汤-活性小分子-靶基因-术后肠梗阻网络,分析大建中汤治疗术后肠梗阻关键靶点以及信号通路;使用脂多糖(LPS)或白介素-4(IL-4)诱导M0 RAW264.7分别向M1或M2型巨噬细胞分化,以大建中汤干预,qRT-PCR、ELISA法检测M1或M2型巨噬细胞因子表达,激光共聚焦检测P65入核情况,蛋白质印迹法(Western blot)检测相关蛋白表达。结果:筛选获得人参皂苷Rh2、人参皂苷Rg1、6-姜酚、6-姜烯酚、羟基-ɑ-山椒素、羟基-β-山椒素、等27个有效化学成分,这些有效成分与POI靶点共有119个交集基因。GO功能富集分析表明大建中汤治疗术后肠梗阻潜在机制与调控蛋白质磷酸化、泛素样蛋白连接酶,调控细胞因子生成有关;KEGG通路富集分析表明大建中汤治疗POI涉及PI3K、AKT、MAPK等通路;大建中汤能够抑制M0型巨噬细胞细胞向M1或M2极化;激光共聚焦及Western blot揭示大建中汤通过调控MAPK通路及NF-κB入核抑制M0型巨噬细胞细胞向M1极化。结论:大建中汤可能通过调控M0型巨噬细胞极化抑制炎症因子的释放而治疗POI。Objective:Network pharmacology and macrophage model of inflammation were used to study the underlying mechanism of Dajianzhong Decoction(大建中汤)in the treatment of postoperative ileus(POI).Methods:The components in Dajianzhong Decoction were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and Traditional Chinese Medicine Integrated Database(TCMID),and active components were screened out based on bioavailability and drug-likeness.The Dajianzhong Decoctionactive component-target gene-POI network was constructed,to analyze the key targets and signaling pathways against POI.Lipopolysaccharide(LPS)or interleukin-4(IL-4)was used to induce the polarization of M0 RAW264.7 into M1 or M2 phenotype,respectively.The expression of M1 or M2 macrophage cytokines was detected by quantitative reverse transcription PCR(qRT-PCR)and enzyme-linked immunosorbent assay(ELISA),and P65 in nucleus by confocal laser scanning microscopy.The expression of relevant proteins was measured by Western blotting.Results:A total of 27 effective components including ginsenoside Rh2,ginsenoside Rg1,6-gingerol,6-shogaol,hydroxy-α-sanshool,and hydroxy-β-sanshool were screened out and these components shared 119 targets with POI.The targets of Dajianzhong Decoction against POI mainly involved the Gene Ontology(GO)terms of positive regulation of protein phosphorylation,ubiquitin protein ligase binding,and positive regulation of cytokine production,and the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways of phosphatidylinositol-3-kinase(PI3K),protein kinase B(AKT),and mitogen-activated protein kinase(MAPK).Dajianzhong Decoction could inhibit the polarization of M0 macrophages to M1 or M2 phenotype.Confocal laser scanning microscopy and Western blotting revealed that Dajianzhong Decoction inhibited the polarization of M0 macrophages to M1 by regulating MAPK pathway and the translocation of nuclear factor kappa B(NF-κB)into the nucleus.Conclusion:Dajianzhong Decoction inhibited the release o

关 键 词：大建中汤 术后肠梗阻 网络药理学 巨噬细胞极化 

分 类 号：R285[医药卫生—中药学]