目的 利用网络药理学和分子对接技术，探究Resolvin D1在治疗颅内出血中的作用机制。方法 自PubChem、TargetNet、Stitch、Disgenet和GeneCards 5个数据库获取了RvD1和颅内出血相关的靶点信息。利用String数据库和Cytoscape软件进行蛋白质相互作用分析和核心靶点筛选，同时进行Go和KEGG富集分析，最后进行分子对接实验验证。 结果 总计获取115个RvD1相关的靶基因和1705个颅内出血靶点，二者交集有60个基因。PPI网络分析结果呈现共60个节点和554条边的复杂网络。前十位核心靶点为IL6、IL1B、TNF、IL10、TLR4、IFNG、STAT3、CD4、MMP9和CCL2。分子对接验证证实RvD1对这些靶蛋白具有较强的结合亲和力。 结论 在颅内出血治疗中RvD1可能通过调节多个靶点基因影响炎症反应和蛋白质结合过程，在多条信号通路中发挥作用。
Abstract
Objective To explore the mechanism of Resolvin D1 in the treatment of intracranial hemorrhage by using network pharmacology and molecular docking techniques. Methods The target information related to RvD1 and intracranial hemorrhage was obtained from five databases: PubChem, TargetNet, Stitch, Disgenet and GeneCards. Then, the protein interaction analysis and core target screening were carried out using String database and Cytoscape software. The enrichment analysis of Go and KEGG was performed at the same time, and finally the molecular docking experiment was conducted for verification. Results A total of 115 RvD1-related target genes and 1705 intracranial hemorrhage targets were obtained, and there were 60 overlapping genes among them. The PPI network analysis results showed a complex network of 60 nodes and 554 edges. The top 10 core targets were IL6, IL1B, TNF, IL10, TLR4, IFNG, STAT3, CD4, MMP9, and CCL2. Molecular docking test showed that RvD1 has strong binding affinity for these target proteins. Conclusions In the treatment of intracranial hemorrhage, RvD1 may affect the inflammatory response and protein binding process by regulating multiple target genes, and plays a role in multiple signaling pathways.
关键词
网络药理学 /
/
/
分子对接 /
/
/
Resolvin D1 /
/
/
颅内出血
Key words
Network pharmacology /
/
/
Molecular docking /
/
/
Resolvin D1 /
/
/
Intracranial hemorrhage
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] Tenny S, Thorell W. Intracranial Hemorrhage[M]. In: StatPearls. Treasure Island (FL): StatPearls Publishing; February 17, 2024. PMID: 29262016.
[2] Sengupta J, Alzbutas R, Falkowski-Gilski P, et al. Intracranial hemorrhage detection in 3D computed tomography images using a bi-directional long short-term memory network-based modified genetic algorithm[J]. Front Neurosci, 2023,17:1200630. DOI:10.3389/fnins.2023.1200630.
[3] Zhou JF, Xiong Y, Kang X, et al. Application of stem cells and exosomes in the treatment of intracerebral hemorrhage: an update[J]. Stem Cell Res Ther, 2022,13(1):281. DOI:10.1186/s13287-022-02965-2.
[4] Li L, Cheng SQ, Sun YQ, et al. Resolvin D1 reprograms energy metabolism to promote microglia to phagocytize neutrophils after ischemic stroke[J]. Cell Rep, 2023,42(6):112617. DOI:10.1016/j.celrep.2023.112617.
[5] Ye Y, Yang Q, Wei J, et al. RvD1 improves resident alveolar macrophage self-renewal via the ALX/MAPK14/S100A8/A9 pathway in acute respiratory distress syndrome[J]. J Adv Res, 2024 Jan 17:S2090-1232(24)00030-34. DOI: 10.1016/j.jare.2024.01.017.
[6] Sun Q, Wang J, Jing Y, et al. Influences of resolvin D1 and D2 on the risk of type 2 diabetes mellitus: a Chinese community-based cohort study[J]. Front Immunol, 2023, 14:1143456. DOI: 10.3389/fimmu. 2023.1143456.
[7] Wen H, Tan J, Tian M, et al. TGF-β1 ameliorates BBB injury and improves long-term outcomes in mice after ICH[J]. Biochem Biophys Res Commun, 2023,654:136-144. DOI: 10.1016/j.bbrc.2023.03.007.
[8] Pierini P, Novelli A, Bossi F, et al. Medical versus neurosurgical treatment in ICH patients: a single center experience[J]. Neurol Sci, 2024,45(1):223-229. DOI: 10.1007/s10072-023-07015-0.
[9] Rose-John S, Jenkins B J, Garbers C, et al. Targeting IL-6 trans-signalling: past, present and future prospects[J]. Nat Rev Immunol, 2023,23(10):666-681. DOI: 10.1038/s41577-023-00856-y.
[10]Lei P, Li Z, Hua Q, et al. Ursolic Acid Alleviates Neuroinflammation after Intracerebral Hemorrhage by Mediating Microglial Pyroptosis via the NF-κB/NLRP3/GSDMD Pathway[J]. Int J Mol Sci, 2023 Sep 30;24(19):14771. DOI: 10.3390/ijms241914771.
[11]Miyakawa AA, Borin TF, Campos L, et al. Activation of Interleukin-1 Beta in Arterialized Vein Grafts and the Influence of the -511C/T IL-1β Gene Polymorphism[J]. J Cardiovasc Dev Dis, 2019 Apr 30;6(2):20. DOI: 10.3390/jcdd6020020.
[12]Sheppard O, Coleman MP, Durrant CS. Lipopolysaccharide-induced neuroinflammation induces presynaptic disruption through a direct action on brain tissue involving microglia-derived interleukin 1 beta[J]. J Neuroinflammation, 2019,16(1):106. DOI: 10.1186/s12974-019-1490-8.
[13]Chédotal H, Narayanan D, Povlsen K, et al. Small-molecule modulators of tumor necrosis factor signaling[J]. Drug Discov Today, 2023,28(6):103575. DOI: 10.1016/j.drudis.2023.103575.
[14]Rowhanirad S, Taherianfard M. The neuroprotective effects of Chalcones from Ashitaba on cuprizone-induced demyelination via modulation of brain-derived neurotrophic factor and tumor necrosis factor α[J]. Brain Behav. 2023;13(9):e3144. DOI:10.1002/brb3.3144.
[15]Tao W, Zhang G, Liu C, et al. Low-dose LPS alleviates early brain injury after SAH by modulating microglial M1/M2 polarization via USP19/FOXO1/IL-10/IL-10R1 signaling[J]. Redox Biol, 2023,66:102863. DOI: 10.1016/j.redox.2023.102863.
[16]Du Y, Wang J, Zhang J, et al. Intracerebral hemorrhage-induced brain injury in mice: The role of peroxiredoxin 2-Toll-like receptor 4 inflammatory axis[J]. CNS Neurosci Ther, 2024,30(3):e14681. DOI: 10.1111/cns.14681.
[17]Liang T, Zhu Z, Gong F, et al. Galectin-3 promotes brain injury by modulating the phenotype of microglia via binding TLR-4 after intracerebral hemorrhage[J]. Aging (Albany NY), 2023,15(17):9041-9058. DOI: 10.18632/aging.205014.
[18]Ng CT, Fong LY, Abdullah M. Interferon-gamma (IFN-γ): Reviewing its mechanisms and signaling pathways on the regulation of endothelial barrier function[J]. Cytokine, 2023,166:156208. DOI: 10.1016/j.cyto.2023.156208.
[19]Gao L, Lu Q, Huang LJ, et al. Transplanted neural stem cells modulate regulatory T, γδ T cells and corresponding cytokines after intracerebral hemorrhage in rats[J]. Int J Mol Sci, 2014,15(3):4431-4441. DOI: 10.3390/ijms15034431.
[20]Zhuang J, Cao Y, Guo G, et al. Inhibition of BACE1 attenuates microglia-induced neuroinflammation after intracerebral hemorrhage by suppressing STAT3 activation[J]. Aging (Albany NY), 2023,15(15):7709-7726. DOI: 10.18632/aging.204935.
[21] Yuan S, Titova OE, Zhang K, et al. Circulating proteins and peripheral artery disease risk: observational and Mendelian randomization analyses[J]. Eur Heart J Open, 2023,3(3):oead56. DOI: 10.1093/ehjopen/oead056.
[22]Feng D, Zhou J, Liu H, et al. Astrocytic NDRG2-PPM1A interaction exacerbates blood-brain barrier disruption after subarachnoid hemorrhage[J]. Sci Adv, 2022,8(39):eabq2423. DOI: 10.1126/sciadv.abq2423.
[23]Liu Y, Wang F, Li Z, et al. Neuroprotective Effects of Chlorogenic Acid in a Mouse Model of Intracerebral Hemorrhage Associated with Reduced Extracellular Matrix Metalloproteinase Inducer[J]. Biomolecules, 2022;12(8):1020. Published 2022 Jul 22. DOI:10.3390/biom12081020.
[24]Guo F, Xu D, Lin Y, et al. Chemokine CCL2 contributes to BBB disruption via the p38 MAPK signaling pathway following acute intracerebral hemorrhage[J]. FASEB J, 2020,34(1):1872-1884. DOI: 10.1096/fj.201902203RR.
基金
云南省地方本科高校基础研究联合专项重点项目（NO. 202101AN070028）；云南省李云庆专家工作站（No.202005AF150014）
PDF(4915 KB)
京ICP备08002354号-3
