乳腺熏洗方促进非哺乳期乳腺炎术后创面愈合网络药理学分析及临床验证  

Network Pharmacology Study on Mechanism of Ruxian Xunxi Prescription in Treating Postoperative Wound Healing After Non-Puerperal Mastitis Surgery and Clinical Verification

作　　者：周悦[1] 王铮 叶媚娜[1] 吴晶晶[1] 何斌俊 陈红风[1] ZHOU Yue;WANG Zheng;YE Meina;WU Jingjing;HE Binjun;CHEN Hongfeng(Longhua Hospital Shanghai University of Traditional Chinese Medicine,Shanghai 200032,China;Ruijin Hospital Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China)

机构地区：[1]上海中医药大学附属龙华医院,上海200032 [2]上海交通大学医学院附属瑞金医院,上海200025

出　　处：《新中医》2024年第6期186-194,共9页New Chinese Medicine

基　　金：上海市闵行区卫健委“龙华医院-闵行”中医外科乳腺专科联盟项目(LM05);龙华医院“科技创新培育计划”项目(PY2022016)。

摘　　要：目的:采用网络药理学方法分析乳腺熏洗方促进非哺乳期乳腺炎(NPM)术后创面愈合的机制,并通过临床研究对关键通路进行验证。方法:利用中药系统药理学数据库与分析平台(TCMSP)检索并筛选乳腺熏洗方的主要化合物成分和作用靶点,在人类基因综合分析数据库(Genecards)中查找与乳房创面愈合相关的共同靶点,将共同靶点输入STRING数据库,获得蛋白质相互作用(PPI)网络,再使用Cytoscape 3.10.10软件绘制PPI网络图。利用DAVID数据库和Metascap数据库对疾病-药物潜在靶点进行基因本体(GO)功能富集分析及京都基因与基因组百科全书(KEGG)通路富集分析。采用蛋白质印迹法检测4例NPM术后患者治疗前后创面组织血管内皮生长因子(VEGF)、信号转导和转录激活蛋白3(STAT3)蛋白表达水平。结果:乳腺熏洗方促进乳房创面愈合共涉及101个靶点,关键靶点有基质金属蛋白酶(MMP2、MMP9)、细胞因子[白细胞介素(IL)-1β、IL-6、表皮生长因子受体(EGFR)、转化生长因子-β(TGF-β)、肿瘤坏死因子(TNF)、成纤维细胞生长因子2(FGF-2)]、黏附分子(ICAM-1)和信号转导蛋白(STAT3、MAPK)等,参与了包括VEGF、缺氧诱导因子-1(HIF-1)、IL-17、AGE-RAGE、TNF等信号通路的调控。治疗后,NPM术后创面组织的VEGF、STAT3蛋白表达水平均较治疗前升高(P<0.05)。结论:乳腺熏洗方通过多途径、多靶点的协同调节,在促进NPM术后创面愈合方面具有明确作用。Objective:To explore action mechanism of Ruxian Xunxi Prescription(a prescription for fumigation and washing on breast)in treating postoperative wound healing after non-puerperal mastitis(NPM)surgery using network pharmacology,and verify key signaling pathways through clinical research.Methods:The key compound components and action targets of Ruxian Xunxi Prescription were searched in the Traditional Chinese Medicines Systems Pharmacology Platform(TCMSP).Common targets associated with breast wound healing were identified in the Human Gene Database(Genecards),which were entered into STRING database to obtain the protein-protein interaction(PPI)networks,and the PPl networks were then mapped via Cytoscape 3.10.10 software.Gene ontology(GO)function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed for potential disease-medicine targets through DAVID and Metascap databases.The protein expression levels of vascular endothelial growth factor(VEGF)and signal transducers and activators of transcription 3(STAT3)were detected by Western Blot in four patients after NPM surgery.Results:There were 101 targets involved in promoting wound healing with Ruxian Xunxi Prescription,among which the key targets were mainly divided into matrix metalloproteinases(MMP2,MMP9),cytokines[interleukin(IL)-1β,IL-6,epidermal growth factor receptor(EGFR),transforming growth factor-β(TGF-β),tumor necrosis factor(TNF),fibroblast growth factor 2(FGF-2)],adhesion molecules(ICAM-1)and signal transduction protein(STAT3,MAPK),ect.,involving in the regulation of signaling pathways such as VEGF,hypoxia-inducible factor-1(HIF-1),IL-17,AGE-RAGE,TNF,etc.:After treatment,the protein expression levels of VEGF and STAT3 in wound tissues after NPM surgery were increased when compared with those before treatment(P<0.05).Conclusion:Network pharmacology and clinical studies have confirmed that Ruxian Xunxi Prescription exerts a curative effect on promoting postoperative wound healing after NPM surgery

关 键 词：非哺乳期乳腺炎 创面愈合 乳腺熏洗方 中药熏洗疗法 网络药理学 信号通路 临床验证 

分 类 号：R655.8[医药卫生—外科学]