[1]李夏,王元博,李欣,等.开心散治疗抑郁症与抑郁合并心肌梗死差异机制网络药理学研究及关键靶点验证[J].西部中医药,2024,37(05):24-36.[doi:10.12174/j.issn.2096-9600.2024.05.04]
　LI Xia,WANG Yuanbo,LI Xin,et al.Pharmacological Study and Key Target Validation of the Mechanism of Difference between Kaixin San for Depression, and Depression Combined with Myocardial Infarction[J].Western Journal of Traditional Chinese Medicine,2024,37(05):24-36.[doi:10.12174/j.issn.2096-9600.2024.05.04]
点击复制

开心散治疗抑郁症与抑郁合并心肌梗死差异机制网络药理学研究及关键靶点验证
分享到：

《西部中医药》[ISSN:2096-9600/CN:62-1204/R]

卷:
37
期数:
2024年05期
页码:
24-36
栏目:
基础研究
出版日期:
2024-05-15

文章信息/Info

Title:
Pharmacological Study and Key Target Validation of the Mechanism of Difference between Kaixin San for Depression, and Depression Combined with Myocardial Infarction
作者:
李夏, 王元博, 李欣, 胡园
中国人民解放军总医院，北京 100089
Author(s):
LI Xia, WANG Yuanbo, LI Xin, HU Yuan
Chinese PLA General Hospital, Beijing 100089, China
关键词:
抑郁症; 抑郁症合并心肌梗死; 开心散; 网络药理学
Keywords:
depression; depression combined with myocardial infarction; network pharmacology
分类号:
R2-03
DOI:
10.12174/j.issn.2096-9600.2024.05.04
文献标志码:
A
摘要:
目的采用网络药理学方法探讨开心散治疗抑郁症和抑郁症合并心肌梗死（myocardial infarction，MI）的主要成分、作用靶点、传导通路和作用机制的异同并对关键靶点进行实验验证。 方法基于公共数据库结合ADME算法筛选开心散有效成分和作用靶点；通过DisGeNET数据库筛选抑郁症和MI及其共病靶点；利用STRING 11.0数据库构建蛋白-蛋白互作（protein-protein interactions，PPI）网络；通过核心靶基因导入基因功能注释数据库（the database for annotation，visualization and integrated discovery，DAVID）进行京都基因与基因组百科全书（kyoto encyclopedia of genes and genomes，KEGG）靶点相关通路分析；通过Cytoscape构建“药物成分-靶点-通路”网络；分析药物成分血脑屏障通过性，并采用Autodock Vina软件进行分子对接验证；建立抑郁症体外模型，采用蛋白质免疫印迹法（western blot，WB）对关键蛋白表达进行验证。 结果筛选出抑郁症与MI共同靶点28个；开心散主要成分30种，治疗抑郁症潜在靶点36个，其中关键靶点为Akt1、TNF、MAPK8、JUN、PTGS2、IL1B、IFNG、GSK3B、NOS2、DRD1等；开心散治疗抑郁症合并MI的主要成分14种，共同作用关键靶点为Akt1、TNF、IL1B、GSK3B、NOS2、BAX、NR3C2、NOS3、ESR1、ADRB1；开心散治疗抑郁症的成分较治疗抑郁症合并MI共同成分具有更强的血脑屏障通过性；分子对接结果显示山柰酚作用于Akt1靶点，参与调控PI3K/Akt通路；体外实验证实山柰酚可上调抑郁模型细胞Akt1蛋白表达。 结论开心散治疗抑郁症和抑郁症合并MI成分和靶点既有相同之处也有不同之处，体现“异病同治”的特点，且其治疗抑郁症主要侧重于对中枢神经系统和内分泌系统的调节，验证实验证实开心散对于治疗抑郁症和抑郁症合并MI具有有效性。
Abstract:
ObjectiveTo investigate the similarities and differences in the main components, targets, conduction pathways and mechanisms of action of Kaixinsan (KXS) in the treatment of depression, and depression combined with myocardial infarction (MI) using network pharmacology and to validate the key targets using the experiments. MethodsThe active ingredients and the targets of KXS were screened based on public database and ADME algorithm; depression and MI, and the shared targets between the diseases were screened from DisGeNET database; protein-protein interaction was constructed using STRING 11.0; KEGG targets related pathways were analyzed using DAVID database; "component-target-pathway" network was constructed by Cytoscape; the blood-brain barrier permeability of drug components was analyzed, and "molecule-key target" docking was verified by Autodock Vina software; the cell model was established, and the expression of key proteins was verified using western blot method. Resultsthere were 28 co-morbid targets of depression and myocardial infarction identified; 30 main components of KXS, and 36 potential targets for depression treatment, among them, the key targets including Akt1, TNF, MAPK8, JUN, PTGS2, IL1B, IFNG, GSK3B, NOS2, DRD1, etc.; 14 main components of KXS involved in the treatment of depression-combined with myocardial infarction and key targets of the co-morbid disease were Akt1, TNF, IL1B, GSK3B, NOS2, BAX, NR3C2, NOS3, ESR1, ADRB1; the components of KXS for the treatment of depression have stronger blood-brain barrier passage than those for the treatment of depression and MI; molecular docking predicts that kaempferol can potentially initiate Akt1 targets and participate in the regulation of PI3K/Akt1 pathway; experiments have confirmed that the ingredient could up-regulate cellular expressions of Akt1 in depression model. ConclusionKXS has both the same and different components and targets in the treatment of depression, and depression combined with myocardial infarction, reflecting part of its scientific connotation of "treating different diseases with the same treatment", and the main focus of treating depression is on the regulation of the central nervous system and endocrine system, which has verified the effectiveness of KXS in the treatment of depression and depression complicating myocardial infarction.

相似文献/References:

[1]寇宁,张玉香,王一强,等.温肾胶囊对抑郁大鼠模型性功能的影响[J].西部中医药,2013,26(05):12.
　KOU Ning,ZHANG Yuxiang,WANG Yiqiang,et al.Effects of W enShen Capsule on Sexual Function of Depressed Rat Model[J].Western Journal of Traditional Chinese Medicine,2013,26(05):12.
[2]马元业,周东林,胡建军,等.度洛西汀联合针刺治疗伴疼痛症状抑郁症64例[J].西部中医药,2015,28(02):108.
[3]彭晓明,陈林庆△,张震文,等.温肾胶囊联合盐酸曲唑酮治疗抑郁症伴勃起功能障碍的临床研究*[J].西部中医药,2012,25(12):4.
　PENG Xiao-ming,CHEN Lin-qing,ZHANG Zhen-wen,et al.Clinical Study on WenShen Capsule and Trazodone Hydrochloride in the Treatment for Depression Complicated with Erectile Dysfunction[J].Western Journal of Traditional Chinese Medicine,2012,25(05):4.
[4]周玉英,李向丽,潘虹,等.抑郁症睡眠障碍患者中医辨证施护效果观察[J].西部中医药,2015,28(07):149.
[5]乐晶晶,易韬,李霁,等.针灸治疗抑郁症的临床研究概况[J].西部中医药,2015,28(10):143.
[6]陈云志,陈家旭,秦忠,等.从维生素D轴探讨巴戟天抗抑郁症的作用机制[J].西部中医药,2017,30(10):128.
　CHEN Yunzhi,CHEN Jiaxu,QIN Zhong,et al.The Discussion on the Anti-depression Mechanism of BaJiTian from Vitamin D Axis[J].Western Journal of Traditional Chinese Medicine,2017,30(05):128.
[7]张军红,许影,拜争刚,等.整体护理对老年抑郁症患者临床疗效影响的系统评价[J].西部中医药,2016,29(07):72.
　ZHANG Junhong,XU Ying,BAI Zhenggang,et al.Systematic Evaluation of Holistic Nursing on Clinical Effects of the Elderly Patients with Depression[J].Western Journal of Traditional Chinese Medicine,2016,29(05):72.
[8]牟秋杰,秦萍萍,刘俊彤,等.李志刚教授“通督启神”法针刺治疗抑郁症经验[J].西部中医药,2018,31(05):25.
　MOU Qiujie,QIN Pingping,LIU Juntong,et al.Professor Li Zhigang′s Clinical Experiences of Treating Depression with ″TongDu QiShen″ Needling[J].Western Journal of Traditional Chinese Medicine,2018,31(05):25.
[9]张妍菀,杨冬榕,李艳,等.中医心理低阻抗意念导入疗法对抑郁症患者的影响[J].西部中医药,2019,32(05):60.
　ZHANG Yanwan,YANG Dongrong,LI Yan,et al.The Effects of Low Resistance Thought Induction Psychotherapy on Depression[J].Western Journal of Traditional Chinese Medicine,2019,32(05):60.
[10]李慧,郝银丽.《黄帝内经》“治未病”在阈下抑郁防治中的应用[J].西部中医药,2020,33(02):141.[doi:10.12174/j.issn.1004-6852.2020.02.40]
　LI Hui,HAO Yinli.The Application of "Preventive Treatment of Disease" in Huangdi Neijing to the Prevention and Treatment of Subthreshold Depression[J].Western Journal of Traditional Chinese Medicine,2020,33(05):141.[doi:10.12174/j.issn.1004-6852.2020.02.40]

备注/Memo

备注/Memo:
李夏（1991—），男，硕士学位，医师。研究方向：神经精神药理学研究。国家自然科学基金（81973502）；国家社会科学基金（22CZJ004）。
更新日期/Last Update: 2024-05-15