|
|
基于整合药理学的乳酸改善小鼠焦虑作用及机制研究
|
Abstract:
目的：基于网络药理学方法探究乳酸改善焦虑的主要靶点及信号通路,结合行为学初步研究其潜在作用机制方法：通过Swiss Target Prediction、Target Net、Sea数据库获得乳酸作用靶点；通过Gene Cards、OMIM、CTD数据库获得焦虑靶点；通过Gene Cards和OMIM建立乳酸和焦虑症的靶基因集用韦恩图显示；通过STRING数据库构建乳酸与焦虑蛋白互作PPI网络图，利用DAVID数据库进行GO功能富集与KEGG通路富集分析。基于网络药理学预测的通路结果，将雄性ICR小鼠随机成溶媒组、乳酸组，每组10只，进行旷场实验，在实验前1 h腹腔注射乳酸或溶媒，记录在旷场实验中进入中间区域的时间和活动度并计算辨别指数。结果：通过Swiss Target Prediction、Target Net、Sea数据库共获得乳酸作用靶点248个；通过Gene Cards、OMIM、CTD数据库共获得焦虑靶点717个；靶点经与Gene Cards和OMIM综合数据库比对，共获取28个乳酸与焦虑的交集基因。结论：乳酸主要通过调控MAO-A信号通路进一步调节5-HT代谢，以及调控苯丙氨酸和酪氨酸代谢与cAMP信号通路及相应的基因表达进一步调节儿茶酚胺类神经递质代谢发挥抗焦虑作用。
Objective: To explore the main targets and signal pathways of lactic acid for improving anxiety based on the method of network pharmacology, and to study its potential mechanism of action in combination with behavioral studies. Methods: Obtain lactic acid targets through Swiss Target Prediction, Target Net, and Sea databases; obtain anxiety targets through Gene Cards, OMIM, and CTD databases; establish lactic acid and anxiety target gene sets through Gene Cards and OMIM; display with Venn diagram; construct lactic acid through STRING database. It interacts with anxiety protein as a PPI network diagram, and uses DAVID database for GO function enrichment and KEGG pathway enrichment analysis. Based on the results of network pharmacology, Male ICR mice were randomly divided into a vehicle group and a lactic acid group, each with 10 mice, and an open field experiment was performed. Lactic acid or vehicle was injected into the abdominal cavity 1 hour before the experiment and the time and activity of entering the middle area in the open field experiment were recorded and the discrimination was calculated. Index. Results: A total of 248 lactic acid targets were obtained through Swiss Target Prediction, Target Net, and Sea databases; a total of 717 anxiety targets were obtained through Gene Cards, OMIM, and CTD databases; a total of 28 lactic acid targets were obtained by comparison with Gene Cards and OMIM comprehensive databases. The intersection gene with anxiety. Conclusion: Lactic acid mainly regulates 5-HT metabolism by regulating the MAO-A signaling pathway, as well as regulating the metabolism of phenylalanine and tyrosine, the cAMP signaling pathway and the corresponding gene expression to further regulate the metabolism of catecholamine neurotransmitters to exert anti-anxiety effects.
| [1] | Zhi, H., Lin, P., Fang, Z., Liu, H., Zhang, R.-H. and Bai, W. (2021) Sea Surface Salinity-Derived Indexes for Distin-guishing Two Types of El Ni?o Events in the Tropical Pacific. Science China Earth Sciences, 64, 1267-1284.
http://kns.cnki.net/kcms/detail/11.5843.P.20210630.1538.007.html
https://doi.org/10.1007/s11430-020-9780-2 |
| [2] | Bonomi, C.G., De Lucia, V., Mascolo, A.P., Assogna, M., Mot-ta, C., Scaricamazza, E., et al. (2021) Brain Energy Metabolism and Neurodegeneration: Hints from CSF Lactate Levels in Dementias. Neurobiology of Aging, 105, 333-339. https://doi.org/10.1016/j.neurobiolaging.2021.05.011 |
| [3] | Morozov Eugene, G. and Frey Dmitry, I. (2021) CTD Data over a Repeated Section in the Vema Channel. Data in Brief, 37, Article ID: 107211. https://doi.org/10.1016/j.dib.2021.107211 |
| [4] | Tkatchenko Tatiana, V. and Tkatchenko Andrei, V. (2021) Genetic Network reGulating Visual Acuity Makes Limited Contribution to Visually Guided Eye Emmetropization. Genomics, 113, 2780-2792.
https://doi.org/10.1016/j.ygeno.2021.06.021 |
| [5] | 苟泽鹏, 董悦, 闫一帆, 王成军. 数据科学的浪潮: 计算社会科学研究综述[J]. 科学？经济？社会, 2021, 39(2): 16-31. |
| [6] | Reeta, M. (2021) Psychological Approach to Aid People with Anxiety Disorder. Clinical and Experimental Psychology, 7, 1. |
| [7] | Kim, S., Chen, J., Cheng, T., Gindulyte, A., He, J., He, S., et al. (2021) PubChem in 2021: New Data Content and Improved Web Interfaces. Nucleic Acids Research, 49, D1388-D1395. https://doi.org/10.1093/nar/gkaa971 |
| [8] | Mayr, F., M？ller, G., Garscha, U., Fischer, J., Rodríguez Casta？o, P., Inderbinen, S.G., et al. (2020) Finding New Molecular Targets of Familiar Natural Products Us-ing in Silico Target Prediction. International Journal of Molecular Sciences, 21, Article No. 7102. https://doi.org/10.20944/preprints202007.0495.v1 |
| [9] | 单柏溪. 基于代谢组与肠道菌群结构特征的酒制五味子抗焦虑作用机制研究[D]: [硕士学位论文]. 南昌: 江西中医药大学, 2020. |
| [10] | 陈芳玲. GLT-1依赖的星形胶质细胞源性乳酸介导氯胺酮抗抑郁效应[D]: [硕士学位论文]. 衡阳: 南华大学,2020. |
| [11] | 张亮. 乳酸抗抑郁效应及其cAMP-BDNF通路机制研究[D]: [硕士学位论文]. 衡阳: 南华大学, 2020. |
| [12] | 龙珊. GLT1依赖的星形胶质细胞糖原源性乳酸介导Apelin-13的抗抑郁效应[D]: [硕士学位论文]. 衡阳: 南华大学, 2020. |
| [13] | Zhao, F.Y., Yan, H.X., Zhao, Y.X., Xu, H., Hong, Y.-F., Ma, Q.-Y., et al. (2020) Effects of Electroacupuncture on the Behaviors and Expressions of Hippocampal Neurotransmitters and Bax/Bcl-2 Proteins in Rat Models of Anxiety Disorder. Journal of Acupuncture and Tuina Science, 18, 83-89. https://doi.org/10.1007/s11726-020-1160-5 |
| [14] | 刘瑞影. 油菜高光效基因挖掘及功能分析[D]: [硕士学位论文]. 重庆: 西南大学, 2020. |
| [15] | Inagaki, R., Moriguchi, S. and Fukunaga, K. (2020) Kir6.1 Heterozygous Mice Exhibit Aberrant Amygdala-Dependent Cued Fear Memory. Molecular Neurobiol-ogy, 57, 1622-1635. https://doi.org/10.1007/s12035-019-01840-1 |
| [16] | Kambe, J., Watcharin, S., Makioka-Itaya, Y., Inoue, R., Watanabe, G., Yamaguchi, H. and Nagaoka, K. (2020) Heat-Killed Enterococcus fecalis (EC-12) Supple-ment Alters the Expression of Neurotransmitter Receptor Genes in the Prefrontal Cortex and Alleviates Anxiety-Like Behavior in Mice. Neuroscience Letters, 720, Article ID: 134753.
https://doi.org/10.1016/j.neulet.2020.134753 |
| [17] | 陈兆斌, 张博, 刘秀敏, 黄树明. 焦虑症发病机制的研究进展[J]. 天津中医药, 2018, 35(4): 316-320. |
| [18] | 董界, 姚志江, 曹东升. TargetNet: 多靶点QSAR预测潜在的药物-靶点相互作用的在线计算平台[C]//中国化学会. 中国化学会第14届全国计算(机)化学学术会议暨分子模拟国际论坛会议手册. 南京: 南京大学, 2017: 160. |
| [19] | Peall, K.J., Lorentzos, M.S., Heyman, I., Tijssen, M.A.J., Owen, M.J., Dale, R.C., et al. (2017) A Review of Psychiatric Co-Morbidity Described in Genetic and Immune Mediated Movement Disorders. Neuroscience & Biobehavioral Reviewss, 80, 23-35. https://doi.org/10.1016/j.neubiorev.2017.05.014 |
| [20] | 毛丽娜, 朱清, 李俊旭. 牡荆素的神经保护作用及机制研究进展[J]. 中国药理学通报, 2016, 32(10): 1353-1356. |
| [21] | 罗旭艳, 欧灿纯, 龚俊, 朱金芳. 南宁市第五人民医院2012-2014年度抗精神病药物使用情况分析[J]. 医药导报, 2016, 35(z1): 142-144. |
| [22] | Yu, X.W., Pandey, K., Katzman, A.C. and Alberini, C.M. (2020) A Role for CIM6P/IGF2 Receptor in Memory Consolidation and Enhance-ment. eLife, 9, Article ID: e54781. |
| [23] | Geddes Sean D., Saleha, A., Lemelin, D., Sokolovski, A., Bergeron, R., Haj Dahmane, S. and Bé？que, J.C. (2016) Target-Specific Modulation of the Descending Prefrontal Cortex Inputs to the Dorsal Raphe Nucleus by Cannabinoids. Proceedings of the National Academy of Sciences of the United States of Amer-ica, 113, 5429-5434.
https://doi.org/10.1073/pnas.1522754113 |
| [24] | Holmes, R.S. and Goldberg, E. (2009) Computational Analyses of Mammalian Lactate Dehydrogenases: Human, Mouse, Opossum and Platypus LDHs. Computational Biology and Chemistry, 33, 379-385.
https://doi.org/10.1016/j.compbiolchem.2009.07.006 |
| [25] | Holmes, A. (2008) Genetic Variation in Corti-co-Amygdala Serotonin Function and Risk for Stress-Related Disease. Neuroscience & Biobehavioral Reviews, 32, 1293-1314. https://doi.org/10.1016/j.neubiorev.2008.03.006 |
| [26] | von Mering, C., Jensen Lars, J., Snel, B., Hoop-er, S.D., Krupp, M., Foglierini, M., Jouffre, N., Huynen, M.A. and Bork, P. (2005) STRING: Known and Predicted Protein-Protein Associations, Integrated and Transferred across Organisms. Nucleic Acids Research, 33, D433-D437. (Database Issue) https://doi.org/10.1093/nar/gki005 |
| [27] | Glynn, D., Sherman, B.T., Hosack, D.A., Yang, J., Gao, W., Clifford Lane, H. and Lempicki, R.A. (2003) DAVID: Database for Annotation, Visualization, and Integrated Dis-covery. Genome Biology, 4, Article No. P3.
https://doi.org/10.1186/gb-2003-4-5-p3 |
