|
|
基于网络药理学及分子对接探究宣白承气汤治疗脓毒症急性肺损伤作用机制
|
Abstract:
目的：通过网络药理学及分子对接探究宣白承气汤治疗脓毒症急性肺损伤作用机制。方法：检索中药系统药理数据库和分析平台(TCMSP)数据库筛选宣白承气汤复方有关活性成分，将大黄、杏仁、瓜蒌作为有效成分，利用Swiss Target Prediction预测有效成分作用的潜在治疗靶点。通过GeneCards数据库收集脓毒症及急性肺损伤相关的疾病靶点，并制作有效成分靶点和疾病靶点的维恩图，获得宣白承气汤治疗脓毒症急性肺损伤的潜在有效靶点。绘制药物–靶点蛋白–疾病的网络图，利用Cytoscape软件分析每个有效成分在治疗脓毒症急性肺损伤中的重要性。将有效化学成分的潜在治疗靶点蛋白与疾病的靶基因取交集输入3库进行基因本体论(GO)功能分析和京都基因与基因组百科全书(KEGG)通路富集分析，并进行分子对接以验证有效化学成分和作用靶点蛋白之间的分子结合能。结果：筛选获得宣白承气汤有效化学成分46个，潜在治疗靶点580个，治疗脓毒症急性肺损伤潜在靶点275个。拓扑性高的化学成分与靶点蛋白均具有较好的结合力。结论：泽兰黄醇、维生素E、光草甘定、番泻苷E qt能够作用于AKT1、IL6、SRC、EGFR、BCL2、CASP3等靶点，通过调节脓毒症急性肺损伤疾病相关通路如ErbB信号通路、细胞凋亡、人巨细胞病毒感染(HCMV)、催乳素信号通路、cAMP信号通路发挥抗炎以及免疫调节的效果，促进器官功能的康复。
Objective: To investigate the mechanism of action of Xuanbai Chengqi Decoction in treating sepsis-induced acute lung injury using network pharmacology and molecular docking. Methods: The active ingredients of Xuanbai Chengqi Decoction were identified through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Rhubarb, almond, and Fructus Trichosanthis were selected as the effective components. The potential therapeutic targets of these effective components were predicted using the Swiss Target Prediction tool. Disease-related targets for sepsis and acute lung injury were collected from the GeneCards database, and a Venn diagram was created to identify the potential effective targets of Xuanbai Chengqi Decoction in treating sepsis-induced acute lung injury. A drug-target protein-disease network was constructed, and the importance of each effective component in treating sepsis-induced acute lung injury was analyzed using Cytoscape software. The potential therapeutic targets of the effective chemical components were intersected with the disease-related genes and subjected to Gene Ontology (GO) function analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Molecular docking was performed to verify the binding affinity between the effective chemical components and the target proteins. Results: A total of 46 effective chemical components and 580 potential therapeutic targets were identified for Xuanbai Chengqi Decoction. Among these, 275 potential targets were associated with the treatment of sepsis-induced acute lung injury. The chemical components with high topological properties exhibited strong binding affinity with the target proteins. Conclusion: Components such as ligustrazine, vitamin E, glycyrrhizin, and sennoside E qt can act on targets like AKT1, IL6, SRC, EGFR, BCL2, and
| [1] | 曹钰, 柴艳芬, 邓颖, 等. 中国脓毒症/脓毒性休克急诊治疗指南(2018) [J]. 感染、炎症、修复, 2019, 20(1): 3-22. |
| [2] | Perner, A., Cecconi, M., Cronhjort, M., Darmon, M., Jakob, S.M., Pettilä, V., et al. (2018) Expert Statement for the Management of Hypovolemia in Sepsis. Intensive Care Medicine, 44, 791-798. https://doi.org/10.1007/s00134-018-5177-x |
| [3] | Prescott, H.C. and Angus, D.C. (2018) Postsepsis Morbidity. JAMA, 319, 91. https://doi.org/10.1001/jama.2017.19809 |
| [4] | Reinhart, K., Daniels, R., Kissoon, N., Machado, F.R., Schachter, R.D. and Finfer, S. (2017) Recognizing Sepsis as a Global Health Priority—A WHO Resolution. New England Journal of Medicine, 377, 414-417. https://doi.org/10.1056/nejmp1707170 |
| [5] | 占利民, 方林森, 胡德林, 等. 脓毒症相关性急性肺损伤发病机制研究进展[J]. 安徽医药, 2010, 14(6): 722-723. |
| [6] | 吴瑭. 温病条辩[M]. 北京: 人民卫生出版社, 1963. |
| [7] | 时文凤, 曹艳, 曹国胜, 等. 矿物药石膏的研究进展[J]. 中药材, 2021, 44(7): 1793-1796. |
| [8] | 曾健, 李聪, 熊磊, 等. 大黄有效成分及其药理作用研究进展[J]. 山东化工, 2024, 53(10): 135-137+141. |
| [9] | 柏寒, 贺梦媛, 徐洋, 等. 中药苦杏仁研究进展及质量标志物的预测分析[J]. 中华中医药学刊, 2024, 42(9): 199-209. |
| [10] | 滕勇荣, 王连侠, 张永清. 瓜蒌药理研究进展[J]. 齐鲁药事, 2010, 29(7): 417-419. |
| [11] | 王芳, 李明心. 宣白承气汤合大陷胸丸加减治疗脓毒症致急性肺损伤的临床观察[J]. 中国中医急症, 2021, 30(4): 707-710. |
| [12] | Hopkins, A.L. (2008) Network Pharmacology: The Next Paradigm in Drug Discovery. Nature Chemical Biology, 4, 682-690. https://doi.org/10.1038/nchembio.118 |
| [13] | Chou, C.H., Hsu, K.C., Lin, T.E. and Yang, C.R. (2020) Anti-Inflammatory and Tau Phosphorylation-Inhibitory Effects of Eupatin. Molecules, 25, Article No. 5652. https://doi.org/10.3390/molecules25235652 |
| [14] | Parlar, A., Arslan, S.O. and Çam, S.A. (2020) Glabridin Alleviates Inflammation and Nociception in Rodents by Activating BKCa Channels and Reducing NO Levels. Biological and Pharmaceutical Bulletin, 43, 884-897. https://doi.org/10.1248/bpb.b20-00038 |
| [15] | 卢少欢, 龙晓英, 胡燕. 番泻苷的研究进展[J]. 广东药学院学报, 2014, 30(1): 118-122. |
| [16] | Uwazie, J.N., Yakubu, M.T., Ashafa, A.O.T. and Ajiboye, T.O. (2020) Identification and Characterization of Anti-Diabetic Principle in Senna alata (Linn.) Flower Using Alloxan-Induced Diabetic Male Wistar Rats. Journal of Ethnopharmacology, 261, Article ID: 112997. https://doi.org/10.1016/j.jep.2020.112997 |
| [17] | Liu, G., Bi, Y., Wang, R., Shen, B., Zhang, Y., Yang, H., et al. (2013) Kinase AKT1 Negatively Controls Neutrophil Recruitment and Function in Mice. The Journal of Immunology, 191, 2680-2690. https://doi.org/10.4049/jimmunol.1300736 |
| [18] | 刘凯, 贾玲玲, 刘倩, 等. miR-155-5P在脓毒症急性肺损伤时调控肺泡巨噬细胞IL-6、MIP-2的表达对中性粒细胞迁移的影响[J]. 中华重症医学电子杂志(网络版), 2020, 6(2): 198-205. |
| [19] | 周雅琴. miR-590-5p通过靶向可溶性白介素6受体抑制宿主抗病毒应答[D]: [博士学位论文]. 武汉: 武汉大学, 2019. |
| [20] | Chen, Q., Chen, T., Xu, Y., Zhu, J., Jiang, Y., Zhao, Y., et al. (2010) Steroid Receptor Coactivator 3 Is Required for Clearing Bacteria and Repressing Inflammatory Response in Escherichia coli-Induced Septic Peritonitis. The Journal of Immunology, 185, 5444-5452. https://doi.org/10.4049/jimmunol.0903802 |
| [21] | Mu, M., Gao, P., Yang, Q., He, J., Wu, F., Han, X., et al. (2020) Alveolar Epithelial Cells Promote IGF-1 Production by Alveolar Macrophages through TGF-β to Suppress Endogenous Inflammatory Signals. Frontiers in Immunology, 11, Article No. 1585. https://doi.org/10.3389/fimmu.2020.01585 |
| [22] | Meng, C., Wang, S., Wang, X., Lv, J., Zeng, W., Chang, R., et al. (2020) Amphiregulin Inhibits TNF-α-Induced Alveolar Epithelial Cell Death through EGFR Signaling Pathway. Biomedicine & Pharmacotherapy, 125, Article ID: 109995. https://doi.org/10.1016/j.biopha.2020.109995 |
| [23] | Zhang, Z., Chen, Z., Liu, R., Liang, Q., Peng, Z., Yin, S., et al. (2020) Bcl-2 Proteins Regulate Mitophagy in Lipopolysaccharide-Induced Acute Lung Injury via PINK1/Parkin Signaling Pathway. Oxidative Medicine and Cellular Longevity, 2020, Article ID: 6579696. https://doi.org/10.1155/2020/6579696 |
| [24] | Yu, Y., Zhang, Y., Zhang, J., Guan, C., Liu, L. and Ren, L. (2020) Cantharidin‐Induced Acute Hepatotoxicity: The Role of TNF‐α, IKK‐α, Bcl‐2, Bax and Caspase3. Journal of Applied Toxicology, 40, 1526-1533. https://doi.org/10.1002/jat.4003 |
| [25] | Messer, M.P., Kellermann, P., Weber, S.J., Hohmann, C., Denk, S., Klohs, B., et al. (2013) Silencing of FAS, FAS-Associated via Death Domain, or Caspase3 Differentially Affects Lung Inflammation, Apoptosis, and Development of Trauma-Induced Septic Acute Lung Injury. Shock, 39, 19-27. https://doi.org/10.1097/shk.0b013e318277d856 |
| [26] | Rahman, A., Henry, K.M., Herman, K.D., Thompson, A.A., Isles, H.M., Tulotta, C., et al. (2019) Inhibition of ErbB Kinase Signalling Promotes Resolution of Neutrophilic Inflammation. eLife, 8, e50990. https://doi.org/10.7554/elife.50990 |
| [27] | Betsuyaku, T., Ito, Y., Peake, N., Al-Bari, A.A., El-Akabawy, G. and Eid, N. (2024) Enhanced Autophagy and Phagocytosis of Apoptotic Lymphocytes in Splenic Macrophages of Acute Ethanol-Treated Rats: Light and Electron Microscopic Studies. Histology and Histopathology, 39, 853-866. |
| [28] | Kumar, V. (2020) Pulmonary Innate Immune Response Determines the Outcome of Inflammation during Pneumonia and Sepsis-Associated Acute Lung Injury. Frontiers in Immunology, 11, Article No. 1722. https://doi.org/10.3389/fimmu.2020.01722 |
| [29] | Li, X., Huang, Y., Xu, Z., Zhang, R., Liu, X., Li, Y., et al. (2018) Cytomegalovirus Infection and Outcome in Immunocompetent Patients in the Intensive Care Unit: A Systematic Review and Meta-Analysis. BMC Infectious Diseases, 18, Article No. 289. https://doi.org/10.1186/s12879-018-3195-5 |
| [30] | 钟建, 唐志强, 罗林. 人巨细胞病毒再激活在ICU非免疫抑制脓毒症患者中的发生及预后分析[J]. 国际检验医学杂志, 2024, 45(1): 121-125. |
| [31] | 傅强, 杜超, 巩传勇, 王娜. 性激素对严重腹腔感染患者人白细胞-DR抗原和可溶性髓系细胞触发受体-1以及预后的影响[J]. 中国危重病急救医学, 2012, 24(8): 461-464. |
| [32] | Majewski, K., Agier, J., Kozłowska, E. and Brzezińska-Błaszczyk, E. (2017) Serum Level of Cathelicidin LL-37 in Patients with Active Tuberculosis and Other Infectious Diseases. Journal of Biological Regulators and Homeostatic Agents, 31, 731-736. |
| [33] | 朱思哲, 叶成林. 基于生物信息学分析构建免疫相关基因脓毒症预后模型[J]. 医学信息, 2022, 35(15): 1-6+13. |
