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基于数据挖掘和网络药理学探讨中药治疗儿童感染性腹泻的用药规 律及作用机制
陈建芬1,2,李丽娟3,梁倩莹3,莫小兰3,张刚3,阮舒琪1,李培武1
0
(1. 广州中医药大学第一附属医院,广州 510405;2. 广东省第二人民医院天河医院,广州 510507;3. 广州医科大学附属妇女儿童医疗中心,广州 510623)
摘要:
目的:基于数据挖掘和网络药理学方法,探讨中药治疗儿童感染性腹泻的用药规律及作用机制。 方法:收集中国知网、 万方、维普、CBM、PubMed 等数据库中现代文献资料及近现代医家著作中关于儿童感染性腹泻的经验及医案并进行整理筛选, 运用中医传承辅助平台(V3. 0)进行处方药物的频次、证候、四气五味、归经及关联规则、核心组合等规律分析,通过 HIT 2. 0 数 据库获取药物作用靶点,利用 CytoScape 3. 10. 2 软件计算所获取的作用靶点,与人类基因数据库(GeneCards)、疾病基因获取数 据库(DisGeNET)和在线人类孟德尔遗传数据库(OMIM) 筛选出的儿童感染性腹泻靶点相映射并取交集,利用 STRING 及 CytoScape 3. 10. 2 软件对交集靶点构建可视化蛋白相互作用(PPI) 网络模型,利用微生信平台对关键靶点进行基因本体论 (GO)和京都基因与基因组百科全书(KEGG)富集分析。 结果:共纳入儿童感染性腹泻中药处方 323 个,性味以温性甘味药为 主,主要归脾、胃经,使用频率较高的药物为茯苓、白术、甘草、党参、陈皮,高频药对为“茯苓-白术”,通过关联规则和 K-means 聚 类等方法得到 3 组核心药物组合。 高频药物治疗儿童感染性腹泻的关键靶点 26 个,KEGG 通路 161 条。 关键靶点为表皮生长 因子受体(EGFR)、白细胞介素 6(IL-6)、信号转导及转录激活因子 3(STAT3)、酪氨酸激酶受体 2(ERBB2)、干扰素 γ(IFN- γ)、 IL-10、转化生长因子 B1(TGFB1)、信号转导及转录激活因子 1(STAT1)、JANUS 激酶 3(JAK3)、叉头框蛋白 P3(FOXP3)、肿瘤坏 死因子相关激活蛋白(CD40LG),主要信号通路为炎症性肠病、Th7 细胞分化、痢疾、JAK-STAT 等。 结论:“多成分、多靶点、多途 径”的治疗方式是中药治疗儿童感染性腹泻的一大优势。 儿童感染性腹泻的中药治疗以健运脾胃为大法,兼以清热、利湿、消 食、导滞等,核心用药为茯苓、白术,无论在虚证或实证中“健运脾胃”贯穿始终。 本研究挖掘的 3 首新方可能与炎症反应、免疫 调节反应、细胞生长与凋亡等过程相关。
关键词:  儿童感染性腹泻  中药  数据挖掘  网络药理学  多靶点
DOI:10.13407/j.cnki.jpp.1672-108X.2025.03.004
基金项目:国家自然科学基金项目,编号 82003829;国家中医药传承创新中心科研专项,编号 2022ZD01;广东省中医药局科研项目,编号 20222163。
Medication Rules and Mechanism of Traditional Chinese Medicine in the Treatment of Infectious Diarrhea in Children Based on Data Mining and Network Pharmacology
Chen Jianfen1,2 , Li Lijuan3 , Liang Qianyi3 , Mo Xiaolan3 , Zhang Gang3 , Ruan Shuqi1 , Li Peiwu1
(1. The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, China; 2. Guangdong Second provincial Central Hospital Tianhe Hospital, Guangzhou 510507, China;3. Women’ s and Children’ s Medical Center Affiliated to Guangzhou Medical Universty, Guangzhou 510623, China)
Abstract:
Objective: To probe into the medication rules and mechanism of traditional Chinese medicine in the treatment of infectious diarrhea in children based on date mining and network pharmacology. Methods: Modern literature data from databases such as CNKI, Wanfang, VIP, CBM and PubMed, as well as the experiences and medical cases related to infectious diarrhea in children recorded in the works of modern and contemporary physicians, were collected and screened. Traditional Chinese Medicine Inheritance Support Platform (V3. 0) was used to analyze the rules of prescription drugs such as frequency, syndromes, four Qi and five flavors, meridian tropism, association rules, and core combinations. Drug targets were obtained from the HIT 2. 0 database. The obtained targets were calculated by using CytoScape 3. 10. 2 software and mapped and intersected with the targets of infectious diarrhea in children screened from human gene database (GeneCards), DisGeNET and online mendelian inheritance in man (OMIM). The STRING and Cytoscape 3. 10. 2 software were used to construct a visual protein-protein interaction (PPI) network model for the intersection targets. The gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis were performed for key targets by using the Weisengxin platform. Results: A total of 323 traditional Chinese medicine prescriptions in the treatment of infectious diarrhea in children were included. The properties and flavors were mainly warm and sweet, mainly attributed to the spleen and stomach meridians. The drugs with the highest usage frequency were respectively Poria cocos, Atractylodes macrocephala koidz, licorice, Codonopsis radix, Citrus reticulata. The high-frequency drug pair was Poria cocos-Atractylodes macrocephala koidz. Three groups of core drug combination were obtained through methods such as association rules and K-means clustering. There were 26 key targets of high-frequency drugs in the treatment of infectious diarrhea in children and 161 KEGG pathways were obtained. The key targets were epidermal growth factor receptor (EGFR), interleukin 6 ( IL-6), signal transduction and transcriptional activator 3 ( STAT3), tyrosine kinase receptor 2 (ERBB2), and interferon gamma ( IFN-γ), IL-10, transforming growth factor B1 ( TGFB1), signal transduction and transcriptional activator 1 (STAT1), JANUS kinase 3 ( JAK3), forkhead box protein P3 ( FOXP3), tumor necrosis factor-related activator protein (CD40LG). And the main pathways were inflammatory bowel disease, Th7 cell differentiation, malaria, and JAK-STAT signaling pathway. Conclusion: The treatment method with “multiple components, multiple targets and multiple pathways” is the advantage of traditional Chinese medicine in the treatment of infectious diarrhea in children. The treatment of infectious diarrhea in children with traditional Chinese medicine takes strengthening and activating the spleen and stomach as the general principle, and is combined with methods such as clearing heat, draining dampness, promoting digestion, and removing stagnation. The core medications are Poria cocos and Atractylodes macrocephala koidz. Strengthening and activating the spleen and stomach runs through both deficiency syndromes and excess syndromes. The three new prescriptions discussed in this study may be related to inflammatory response, immune regulatory response, cell growth and apoptosis.
Key words:  infectious diarrhea in children  traditional Chinese medicine  data mining  network pharmacology  multiple targets

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