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2025 01 v.36 43-49
黄精活性成分芹菜素对抗尾悬吊模拟失重诱发的大鼠抑郁行为研究
基金项目(Foundation): 中央高校基本科研业务费(D5000230104)
邮箱(Email): qianair@nwpu.edu.cn;
DOI: 10.16289/j.cnki.1002-0837.2025.01008
中文作者单位:

西北工业大学生命学院;

摘要(Abstract):

目的 筛选黄精中的抗抑郁活性化合物,探讨其对模拟失重引起抑郁的防护作用及机制。方法 通过系统药理学筛选黄精中的潜在抗抑郁天然活性成分及其作用靶点。实验采用后肢尾悬吊大鼠模型,将24只健康雄性SD大鼠随机分为对照组(0.5%羧甲基纤维素钠灌胃)、HLU组(尾悬吊组)和HLU+治疗组(尾悬吊+活性化合物灌胃组),每组8只。尾悬吊28 d后,通过强迫游泳实验和悬尾实验评估大鼠的抑郁行为,采用H&E染色观察海马组织形态学变化,分析活性化合物靶点的基因本体(GO)、京都基因和基因组数据库(KEGG)的富集结果。结果 从黄精中筛选出38种活性化合物,其中芹菜素的口服利用度为23.06%,类药性为0.21。芹菜素在化合物–靶点网络中的度值和中介中心性较高,预测其可能是黄精中抗抑郁的关键成分。在强迫游泳和悬尾实验中,HLU组大鼠的不动时间与对照组相比显著增加,表明抑郁模型构建成功;而与HLU组相比,HLU+芹菜素组大鼠的不动时间显著减少。海马组织的H&E染色结果显示,HLU组的大鼠海马神经元细胞数目显著减少,出现较多神经元皱缩,神经纤维出现较多小空泡;而HLU+治疗组的大鼠海马神经元数量增加,细胞形态得到改善。靶点富集分析表明,芹菜素的靶点主要涉及细胞凋亡调控及癌症相关信号通路。结论 芹菜素能够显著改善尾悬吊模拟失重大鼠的抑郁行为,并对海马组织具有保护作用,可能为治疗航天失重导致的抑郁提供一种新的天然活性药物。

关键词(KeyWords): 系统药理学;航天失重;抑郁;行为学实验;海马
参考文献

[1] Marazziti D, Arone A, Ivaldi T, et al. Space missions:Psychological and psychopathological issues[J]. CNS Spectr, 2022, 27(5):536-540.

[2] Van Ombergen A, Demertzi A, Tomilovskaya E, et al. The effect of spaceflight and microgravity on the human brain[J]. J Neurol, 2017,264:S18-S22.

[3] Smith SM, Abrams SA, Davis-Street JE, et al. Fifty years of human space travel:Implications for bone and calcium research[J]. Annual Review of Nutrition, 2014, 34:377-400.

[4] Kishi T, Ikuta T, Sakuma K, et al. Antidepressants for the treatment of adults with major depressive disorder in the maintenance phase:A systematic review and network meta-analysis[J]. Mol Psychiatry,2023, 28(1):402-409.

[5] Kang D, Dong H, Shen Y, et al. The clinical application of chinese herbal medication to depression:A narrative review[J]. Front Public Health, 2023, 11:1120683.

[6] Pan W, Shi H, Zang Z, et al. Research progress on classical traditional chinese medicine formula baihe zhimu(lilium lancifolium bulb and anemarrhena asphodeloides rhizome)decoction in the treatment of depression[J]. Heliyon, 2024, 10(3):e25171.

[7]李彦力,苏艺,袁晚晴,等.黄精主要活性成分、功能及其作用机制研究进展[J].现代食品科技,2023,39(12):354-363.

[8] Jin H, Liu Y, Guo Z, et al. Recent development in liquid chromatography stationary phases for separation of traditional chinese medicine components[J]. J Pharm Biomed Anal, 2016, 130:336-346.

[9] Zhou W, Liu Y, Wang J, et al. Application of two-dimensional liquid chromatography in the separation of traditional chinese medicine[J].J Sep Sci, 2020, 43(1):87-104.

[10] Zhang W, Huai Y, Miao Z, et al. Systems pharmacology for investigation of the mechanisms of action of traditional chinese medicine in drug discovery[J]. Front Pharmacol, 2019, 10:743.

[11] Ru JL, Li P, Wang JN, et al. Tcmsp:A database of systems pharmacology for drug discovery from herbal medicines[J]. J Cheminformatics, 2014, 6:6.

[12] Zhu N, Hou J, Yang N. Network pharmacology integrated with experimental validation revealed the anti-inflammatory effects of andrographis paniculata[J]. Sci Rep, 2021, 11(1):9752.

[13] Yu H, Chen JX, Xu X, et al. A systematic prediction of multiple drugtarget interactions from chemical, genomic, and pharmacological data[J]. PLoS One, 2012, 7(5):14.

[14]林煜,刘宗琳,骞爱荣,等.一种模拟失重性骨丢失小鼠尾悬吊模型的建立[J].航天医学与医学工程,2012,25(4):239-242.

[15] Globus RK, Morey-Holton E. Hindlimb unloading:Rodent analog for microgravity[J]. Journal of applied physiology, 2016, 120(10):1196-1206.

[16]姜宁,张亦文,姚彩虹,等.大小鼠抑郁行为实验方法概述[J].中国实验动物学报,2021,29(6):830-838.

[17] Arauchi R, Hashioka S, Tsuchie K, et al. Gunn rats with glial activation in the hippocampus show prolonged immobility time in the forced swimming test and tail suspension test[J]. Brain Behav, 2018, 8(8):9.

[18]王跃,陈善广,吴斌,等.长期空间飞行任务中航天员出现的心理问题[J].心理技术与应用,2013,1:40-45.

[19] Boaden K, Tomlinson A, Cortese S, et al. Antidepressants in children and adolescents:Meta-review of efficacy, tolerability and suicidality in acute treatment[J]. Front Psychiatry, 2020, 11:717.

[20]陶梦婷,李丽霞,王怀莹,等.黄精、多花黄精、滇黄精的多糖组分及其抗炎、抗氧化作用比较[J].中成药,2023,45(4):1367-1372.

[21]张瑛毓,王丹阳,孙源,等.黄精改善神经功能及产业应用进展[J].食品工业科技,2023, 44(21):450-457.

[22] Li ZH, Yu D, Huang NN, et al. Immunoregulatory mechanism studies of ginseng leaves on lung cancer based on network pharmacology and molecular docking[J]. Sci Rep, 2021, 11(1):18201.

[23] Jin X, Wang H, Liang X, et al. Calycosin prevents bone loss induced by hindlimb unloading[J]. NPJ Microgravity, 2022, 8(1):23.

[24] Yankelevitch-Yahav R, Franko M, Huly A, et al. The forced swim test as a model of depressive-like behavior[J]. J Vis Exp, 2015:97.

[25] Can A, Dao DT, Terrillion CE, et al. The tail suspension test[J]. J Vis Exp, 2012, 59:e3769.

[26]张米佳,王孟迪,Ahmed A,等.模拟失重不同时长对大鼠抑郁样行为的影响(英文)[J].生物化学与生物物理进展,2023,50(2):346-357.

[27] Soltesz I, Losonczy A. CA1 pyramidal cell diversity enabling parallel information processing in the hippocampus[J]. Nat Neurosci, 2018,21(4):484-493.

[28] Wu D, Yang L, Xu XY, et al. Effects of congenital hcmv infection on synaptic plasticity in dentate gyrus(dg)of rat hippocampus[J]. Brain Res, 2011, 1389:27-34.

[29] Bartsch T, Wulff P. The hippocampus in aging and disease:From plasticity to vulnerability[J]. Neuroscience, 2015, 309:1-16.

[30] Tatu L, Vuillier F. Structure and vascularization of the human hippocampus[J]. Frontiers of neurology and neuroscience, 2014,34:18-25.

[31] Kraus C, Castrén E, Kasper S, et al. Serotonin and neuroplasticitylinks between molecular, functional and structural pathophysiology in depression[J]. Neuroscience and biobehavioral reviews, 2017,77:317-326.

[32] Krishnan V, Nestler EJ. The molecular neurobiology of depression[J].Nature, 2008, 455(7215):894-902.

[33] Singh R, Letai A, Sarosiek K. Regulation of apoptosis in health and disease:The balancing act of bcl-2 family proteins[J]. Nat Rev Mol Cell Biol, 2019, 20(3):175-193.

[34] Ruiz NAL, Delángel DS, Olguín HJ, et al. Neuroprogression:The hidden mechanism of depression[J]. Neuropsychiatr Dis Treat, 2018,14:2837-2845.

[35] Zheng C, Liu T, Liu H, et al. Role of bcl-2 family proteins in apoptosis and its regulation by nutrients[J]. Curr Protein Pept Sci,2020, 21(8):799-806.

[36] Xu DH, Du JK, Liu SY, et al. Upregulation of klk8 contributes to cums-induced hippocampal neuronal apoptosis by cleaving ncam1[J].Cell Death Dis, 2023, 14(4):278.

[37] McKernan DP, Dinan TG, Cryan JF."Killing the blues":A role for cellular suicide(apoptosis)in depression and the antidepressant response?[J]. Prog Neurobiol, 2009, 88(4):246-263.

基本信息:

DOI:10.16289/j.cnki.1002-0837.2025.01008

中图分类号:R285.5

引用信息:

[1]邓晓铌,张文娟,余宏等.黄精活性成分芹菜素对抗尾悬吊模拟失重诱发的大鼠抑郁行为研究[J].航天医学与医学工程,2025,36(01):43-49.DOI:10.16289/j.cnki.1002-0837.2025.01008.

基金信息:

中央高校基本科研业务费(D5000230104)

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