| 引用本文: | 黄家望,冯芷莹,王康宇,刘卓琳,马心悦,何清湖,李玲.基于网络药理学和动物实验探讨龟鹿二仙胶治疗非小细胞肺癌的潜在作用途径[J].中国现代应用药学,2025,42(2):20-30. |
| Huang Jiawang,FENG Zhi-ying,WANG Kang-yu,LIU Zhuo-lin,MA Xin-yue,HE Qing-hu,LI Ling.Explore the potential pathways of action of Guilu Erxian Jiao in the treatment of non-small cell lung cancer based on network pharmacology and animal experiments[J].Chin J Mod Appl Pharm(中国现代应用药学),2025,42(2):20-30. |
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| 基于网络药理学和动物实验探讨龟鹿二仙胶治疗非小细胞肺癌的潜在作用途径 |
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黄家望, 冯芷莹, 王康宇, 刘卓琳, 马心悦, 何清湖, 李玲
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湖南中医药大学
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| 摘要: |
| 目的：通过网络药理学预测并结合动物实验验证，探讨龟鹿二仙胶协同顺铂治疗非小细胞肺癌的作用机制。方法：通过TCMSP、HERB、PubChem、Swiss、Genecard、OMIM、PharmGkb 和TTD等数据库，检索并归纳龟鹿二仙胶活性成分、作用靶点及疾病靶点，STRING数据库构建蛋白互作网络，并用Cytoscape3.9.0进行拓扑分析和核心靶点的筛选，使用Cytoscape3.9.0构建药物-成分-靶点-疾病相关网络图，采用R语言进行基因本体 (gene ontology，GO)功能注释、京都基因与基因组百科全书 (Kyoto Encyclopedia of Genes and Genomes，KEGG)富集分析。构建肺原位癌小鼠模型，用苏木精-伊红染色法( hematoxylin-eosin staining，HE )判定模型和给药后各组小鼠肺组织病理学变化，旷场实验评估各组小鼠活动状态和紧张度，实时荧光定量聚合酶链反应法 (Real time-Quantitative polymerase chain reaction)和Western blot法检测各组小鼠肺组织mRNA和蛋白表达情况。结果：共获取龟鹿二仙胶81活性成分和190个作用靶点，6002个非小细胞肺癌作用靶点，共得到149个交集靶点。GO功能注释得出2550条结果，其中生物过程 (biological process，BP)2300条，细胞组成 (cellular component，CC)73条，分子功能 (molecular function，MF)177条。KEGG富集得到相关通路176条，其中缺氧诱导因子1 (hypoxia inducible factor-1, HIF-1) 信号通路具有重要相关性。动物实验发现造模7天后肺癌组小鼠肺组织出现团块状实质性病变，出现部分病理性核分裂，体重较对照组减轻，提示模型构建成功；对各组小鼠体重和饮食进行监测发现，龟鹿二仙胶能增加肺癌小鼠体重和饮食；旷场实验结果表明，龟鹿二仙胶能有效改善小鼠癌因性疲劳，还能有效改善顺铂注射后的不良反应；HE染色发现龟鹿二仙胶能减少小鼠肺组织癌性病理变化；RT-qPCR和Western blot检测发现龟鹿二仙胶能下降小鼠肺组织中缺氧诱导因子1α (hypoxia inducible factor-1α, HIF-1α)、血管内皮生长因子(vascular endothelial growth factor，VEGF)、诱导型一氧化氮合酶(inducible nitric oxide synthase，iNOS)的mRNA和蛋白的表达。结论：龟鹿二仙胶能有效治疗非小细胞肺癌，其治疗具有多成分、多靶点、多通路的特点，且HIF-1信号通路可能其治疗的作用途径之一。 |
| 关键词: 网络药理学 动物实验验证 龟鹿二仙胶 非小细胞肺癌 作用机制 |
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| Explore the potential pathways of action of Guilu Erxian Jiao in the treatment of non-small cell lung cancer based on network pharmacology and animal experiments |
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Huang Jiawang, FENG Zhi-ying, WANG Kang-yu, LIU Zhuo-lin, MA Xin-yue, HE Qing-hu, LI Ling
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Hunan University of traditional Chinese Medicine
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| Abstract: |
| OBJECTIVE Through network pharmacology prediction and animal experiment verification, the mechanism of action of Guilu Erxian Jiao combined with cisplatin in the treatment of non-small cell lung cancer was explored. METHODS The active ingredients, target proteins, and disease targets of Guilu Erxian Jiao were retrieved and summarized from various databases including TCMSP, HERB, PubChem, Swiss, Genecard, OMIM, PharmGkb, and TTD. The protein interaction network was constructed using the STRING database, and the topological analysis and screening of core targets were performed using Cytoscape3.9.0. A drug-ingredient-target-disease network diagram was constructed using Cytoscape3.9.0, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed using R language. A mouse model of lung adenocarcinoma was constructed, and HE staining was used to determine the pathological changes in lung tissue of the model and treatment groups. Open field experiments were performed to evaluate the activity and anxiety of the mice in each group, and RT-qPCR and Western blot were used to detect the mRNA and protein expression in the lung tissue of the mice in each group. RESULTS A total of 81 active ingredients and 190 target proteins of Guilu Erxian Jiao were obtained, as well as 6002 non-small cell lung cancer target proteins, and a total of 149 intersecting targets were identified. GO enrichment analysis yielded 2550 results, including 2300 in the biological process (BP), 73 in the cellular component (CC), and 177 in the molecular function (MF). KEGG enrichment analysis yielded 176 related pathways, among which the HIF-1 signaling pathway was found to be significantly associated. In the animal experiments, it was found that lung cancer mice showed solid pathological changes and partial pathological nuclear division in lung tissue seven days after modeling, and the weight was significantly reduced compared to the control group, indicating the successful establishment of the model. Monitoring of the weight and diet of the mice in each group showed that Guilu Erxian Jiao could increase the weight and diet of the lung cancer mice. The open field test results showed that Guilu Erxian Jiao could effectively improve cancer-related fatigue in mice and also improve adverse reactions after cisplatin injection. HE staining showed that Guilu Erxian Jiao could reduce the pathological changes in lung tissue of the mice. RT-qPCR and Western blotting showed that Guilu Erxian Jiao could down-regulate the mRNA and protein expression of HIF-1α, VEGF, and iNOS in the lung tissue of the mice. CONCLUSION Guilu Erxian Jiao can effectively treat non-small cell lung cancer, and its treatment has the characteristics of multiple components, targets, and pathways, and the HIF-1 signaling pathway may be one of the pathways by which it works. |
| Key words: Network Pharmacology, Animal experimental validation, Guilu Erxianjiao, Non-small cell lung cancer, Mechanism of action |
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