摘要： 目的 应用网络药理学方法，探讨黄连在治疗百草枯中毒导致的急性肝损伤时的潜在相关分子机制。方法 在中药系统药理学数据库与分析平台（TCMSP）中查询并获得黄连活性成分和靶点。通过人类基因数据库GeneCards获取百草枯中毒导致的急性肝损伤的相关靶点基因。采用Cytoscape 3.7软件制作药物-成分-疾病靶点的网络框架图。利用STRING数据库获得交集靶点的蛋白质-蛋白质相互作用网络图。利用DAVID数据库对基因功能和通路富集进行分析。综合考虑靶点和通路富集情况，选取AKT1和p-AKT1进行动物实验验证。结果 共收集黄连活性成分14个，相关作用靶点基因278个，其中与百草枯中毒导致的急性肝损伤的交集靶点基因32个。排名前6位的靶点蛋白是AKT1、TOP1、ErbB2、TLR4、PTGS2、MPO。同时富集到有关的信号通路包括催乳素信号通路、胰腺癌、表皮生长因子受体酪氨酸激酶抑制剂耐药性、FcεRI、膀胱癌、癌症中的中心碳代谢、ErbB信号通路、子宫内膜癌、血管内皮生长因子信号通路等。动物实验结果显示，经过黄连治疗后，百草枯中毒小鼠肝脏病理损伤减轻，炎症指标肿瘤坏死因子-α水平降低，转氨酶水平降低，p-AKT1水平降低。结论 黄连在治疗百草枯中毒导致的急性肝损伤中具有多成分、多靶点、多通路的特点。黄连可降低AKT1蛋白的磷酸化水平，从而对百草枯导致的急性肝损伤发挥治疗作用。

基于网络药理学研究黄连治疗百草枯中毒致急性肝损伤的分子机制

王晓凤, 赵敏

中国医科大学附属盛京医院急诊科, 沈阳 110004

收稿日期:2023-04-21出版日期:2023-08-30发布日期:2023-08-07
通讯作者:赵敏E-mail:min_zhao61@163.com
作者简介:王晓凤(1993-),女,医师,博士研究生.
基金资助:辽宁省自然科学基金（201602879）


关键词: 网络药理学, 黄连, 百草枯中毒, 急性肝损伤, 分子机制
Abstract: Objective To investigate the molecular mechanism of Huanglian for the treatment of paraquat-induced acute liver injury based on network pharmacology. Methods The active ingredients and targets of Huanglian were acquired and screened using the TCMSP database. Paraquat-induced acute liver injury-related targets were obtained using the GeneCards database. Cytoscape 3.7 software was used to make a drug-components-disease targets network. A protein-protein interaction network was obtained using the STRING database. Gene function and pathway enrichment analyses were performed using the DAVID database. Based on the target genes and pathway enrichment analysis results,AKT1 and p-AKT1 were selected for future animal experiments. Results A total of 14 active components that act on 278 target genes were collected. Thirty-two core genes of paraquat-induced acute liver injury and Huanglian were screened. The top six target proteins included AKT1,TOP1,ErbB2,TLR4,PTGS2,and MPO. Pathway enrichment analysis revealed that the prolactin signaling pathway,pancreatic cancer,epidermal growth factor receptor tyrosine kinase inhibitor resistance,FcεRI,bladder cancer,central carbon metabolism in cancer,ErbB,endometrial cancer,vascular endothelial growth factor,and other signaling pathways may participate in the process. Conclusion Huanglian has several components and targets and is involved in various pathways in the treatment of paraquat-induced acute liver injury. Huanglian can reduce the phosphorylation level of AKT1 protein,playing a crucial role in the treatment of paraquat-induced acute liver injury.
Key words: network pharmacology, Huanglian, paraquat poisoning, acute liver injury, molecular mechanism
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