基于网络药理学分析加味归脾汤治疗阴火失眠伴焦虑的机制

刘飞祥; 林子璇; 张怀亮; 杨克勤; 张道培; 徐进; 范晓飞; 王永涛; 李丹; 赵玉男

doi:10.13422/j.cnki.syfjx.20201930

您当前的位置：

首页 >

文章列表页 >

基于网络药理学分析加味归脾汤治疗阴火失眠伴焦虑的机制

数据挖掘 | 更新时间：2020-09-16

- 基于网络药理学分析加味归脾汤治疗阴火失眠伴焦虑的机制
- Analysis on Mechanisms of Modified Guipitang in Treatment of Yin-Fire Insomnia with Anxiety Based on Network Pharmacology
- 中国实验方剂学杂志 2020年26卷第20期页码：161-168
- 作者机构：
  
  1.河南中医药大学第一附属医院，郑州 450000
  2.南京中医药大学医学与生命科学学院，南京 210023
- 作者简介：
  
  刘飞祥，医师，从事中医脑部疾病的研究，E-mail：1353336582@qq.com
  张怀亮，主任医师，从事中医脑部疾病的研究，E-mail：zhl121@126.com
- 基金信息：
  
  吴阶平医学基金会临床科研专项(320.6750.18326);全国名老中医药专家传承工作室建设项目(国中医药人教函[2018]134号)
- DOI：10.13422/j.cnki.syfjx.20201930
  中图分类号： R22;R242;R2-031;R285.5
- 收稿日期：2019-12-05，
  
  网络出版日期：2020-07-23，
  
  纸质出版日期：2020-10-20
- 稿件说明：
移动端阅览
刘飞祥,林子璇,张怀亮等.基于网络药理学分析加味归脾汤治疗阴火失眠伴焦虑的机制[J].中国实验方剂学杂志,2020,26(20):161-168.

LIU Fei-xiang,LIN Zi-xuan,ZHANG Huai-liang,et al.Analysis on Mechanisms of Modified Guipitang in Treatment of Yin-Fire Insomnia with Anxiety Based on Network Pharmacology[J].Chinese Journal of Experimental Traditional Medical Formulae,2020,26(20):161-168.
刘飞祥,林子璇,张怀亮等.基于网络药理学分析加味归脾汤治疗阴火失眠伴焦虑的机制[J].中国实验方剂学杂志,2020,26(20):161-168. DOI： 10.13422/j.cnki.syfjx.20201930.

LIU Fei-xiang,LIN Zi-xuan,ZHANG Huai-liang,et al.Analysis on Mechanisms of Modified Guipitang in Treatment of Yin-Fire Insomnia with Anxiety Based on Network Pharmacology[J].Chinese Journal of Experimental Traditional Medical Formulae,2020,26(20):161-168. DOI： 10.13422/j.cnki.syfjx.20201930.

摘要

目的

借助网络药理学分析技术，探讨加味归脾汤治疗阴火失眠伴焦虑的作用机制。

方法

采用中药系统药理学数据库及分析平台（TCMSP），筛选加味归脾汤的主要化合物成分和药物靶基因；通过GeneCards和人类孟德尔遗传综合数据库（OMIM）建立失眠和焦虑的靶基因集；通过STRING 11.0软件分析交集基因之间的相互作用；采用Cytoscape_3.6.1软件分析和马修斯相关系数（MCC）算法筛选核心基因。基于网络分析结果，将48只SD雌性大鼠随机分配为空白组，模型组，右佐匹克隆片组（0.2 mg·kg

-1

·d

-1

），加味归脾汤低、中、高剂量组（0.31，1.25，5 g·kg

-1

·d

-1

）。采用氯苯丙氨酸（PCPA）腹腔注射方法，建立失眠伴焦虑动物模型，并给予相应药物治疗7 d；然后进行自主活动实验观察大鼠活动的次数、时间和路程；实时荧光定量聚合酶链式反应检测大鼠海马组织中RAC-

丝氨酸/苏氨酸蛋白激酶（Akt1），丝裂原活化蛋白激酶3（MAPK3），丝裂原活化蛋白激酶8（MAPK8）和白细胞介素-6（IL-6）mRNA表达。

结果

从TCMSP数据库中共筛选出228个化合物活性成分；经与GeneCards和OMIM综合数据库比对，共获取181个疾病与药物的交集基因；STRING软件和MCC算法共获得MAPK3，MAPK8，Akt1，IL-6等9个关键基因。动物实验表明，与模型组比较，加味归脾汤高、中剂量组的活动次数、时间和路程显著减少（

0.01），海马组织中MAPK3，MAPK8，Akt1，IL-6 mRNA表达显著降低（

0.01），低剂量组差异无统计学意义。

结论

加味归脾汤治疗阴火失眠伴焦虑作用机制，可能与对MAPK3，MAPK8，Akt1，IL-6基因的调节有关。

Abstract

Objective

To explore the mechanism of modified Guipitang in the treatment of Yin-Fire insomnia with anxiety with the help of network pharmacological analysis technology.

Method

Traditional Chinese Medicine Systems Pharmacology (TCMSP) was used to screen the main components and target genes of modified Guipitang. GeneCards and Online Mendelian Inheritance in Man (OMIM) were used to establish the target gene sets of insomnia and anxiety. STRING 11.0 software was used to analyze the interaction between the overlapping genes

and Cytoscape_3.6.1 software analysis and Matthews correlation coefficient (MCC) algorithm were used to screen the core genes. Based on the results of network analysis

48 SD female rats were randomly divided into blank control group

model group

eszopiclone tablets group (0.2 mg·kg

-1

·d

-1

)

modified Guipitang low，medium，and high-dose groups (0.31，1.25，5 g·kg

-1

·d

-1

). The model of insomnia with anxiety was established by intraperitoneal injection of Para-chlorophenylalanine (PCPA) and these rats were treated with corresponding drugs for 7 days. Then the frequency

time and distance of the activities were observed in the experiment of autonomic activity. Real-time quantitative polymerase chain reaction (PCR) was used to detect the mRNA expressions of proactivated protein kinase 8 (MAPK8)

RAC-alpha serine/threonine protein kinase (Akt1)

mitogen-activated protein kinase 3 (MAPK3) and interleukin-6 (IL-6) in rat hippocampus.

Result

A total of 228 active compounds were screened from TCMSP database and 181 intersecting genes of diseases and drugs were obtained by comparing with GeneCards and OMIM comprehensive database. 9 core genes

including MAPK3

MAPK8

Akt1 and IL-6 were identified by STRING software and MCC algorithm. Animal experiments showed that the number of activity times

time and distance of modified Guipitang in high and medium dose groups were significantly lower than those in the model group. The high and middle dose groups of modified Guipitang could significantly inhibit the mRNA expression of MAPK3

MAPK8

Akt1 and IL-6 in hippocampus（

0.01）

while the low dose group had no significant effect.

Conclusion

The mechanism of modified Guipitang in treating Yin-fire insomnia with anxiety may be related to the regulation of MAPK3

MAPK8

Akt1 and IL-6 genes.

关键词

Keywords

references

JANSEN R P , WATANABE K , STRINGER S , et al . Genome-wide analysis of insomnia in 1,331,010 individuals identifies new risk loci and functional pathways [J]. Nat Genet , 2019 , 51 ( 3 ): 394 - 403 .

ZHENG W , LUO X N , LI H Y , et al . Regional differences in the risk of insomnia symptoms among patients from general hospital outpatient clinics [J]. Neuropsychiatr Dis Treat , 2018 , doi: 10.2147/NDT.S184216 http://dx.doi.org/10.2147/NDT.S184216 .

MIKOLAJEWSKI A J , SCHEERINGA M S , WEEMS C F . Evaluating diagnostic and statistical manual of mental disorders, fifth edition posttraumatic stress disorder diagnostic criteria in older children and adolescents [J]. J Child Adolesc Psychopharmacol , 2017 , 27 ( 4 ): 374 - 382 .

BAXTER A J , SCOTT K M , VOS T , et al . Global prevalence of anxiety disorders: a systematic review and meta-regression [J]. Psychol Med , 2013 , 43 ( 5 ): 897 - 910 .

NÉMETH G , LASZLOVSZKY I , CZOBOR P , et al . Cariprazine versus risperidone monotherapy for treatment of predominant negative symptoms in patients with schizophrenia: a randomised, double-blind, controlled trial [J]. Lancet , 2017 , 389 ( 10074 ): 1103 - 1113 .

SMITH M T , MCCRAE C S , CHEUNG J , et al . Use of actigraphy for the evaluation of sleep disorders and circadian rhythm sleep-wake disorders: an American academy of sleep medicine clinical practice guideline [J]. J Clin Sleep Med , 2018 , 14 ( 7 ): 1231 - 1237 .

谢光璟 , 黄攀攀 , 王平 . 天王补心丹加减改善PCPA失眠大鼠Trx系统氧化损伤的机制探讨 [J]. 中国实验方剂学杂志 , 2019 , 25 ( 6 ): 32 - 38 .

蔡艳 , 叶玉妹 , 张涛 , 等 . 桂枝甘草龙骨牡蛎汤加减治疗阴虚火旺型更年期失眠疗效及对患者睡眠质量、神经递质的影响 [J]. 中国实验方剂学杂志 , 2019 , 25 ( 9 ): 38 - 42 .

刘贯华 , 闫东艳 , 张怀亮 . 张怀亮应用三调汤、四调汤经验 [J]. 中国民间疗法 , 2018 , 26 ( 12 ): 50 - 51 .

秦合伟 , 张怀亮 . 张怀亮教授论治失眠的思想探析 [J]. 光明中医 , 2010 , 25 ( 1 ): 13 - 14 .

王永涛 , 张怀亮 . 相火、阴火、龙雷之火、浮游之火统一论 [J]. 国医论坛 , 2019 , 34 ( 4 ): 10 - 11 .

魏砚君 , 卞宏生 , 叶晓楠 , 等 . 睡眠剥夺动物模型及其在中医药改善睡眠研究中的应用 [J]. 中国实验方剂学杂志 , 2018 , 24 ( 10 ): 227 - 234 .

陈裕曦 . 《脾胃论》中失眠病机治则浅析 [J]. 亚太传统医药 , 2017 , 13 ( 18 ): 35 - 36 .

HUI L , BAKIRI L , MAIRHORFER A , et al . P38alpha suppresses normal and cancer cell proliferation by antagonizing the JNK-c-Jun pathway [J]. Nat Genet , 2007 , 39 ( 6 ): 741 - 749 .

FAN H Y , LIU Z , SHIMADA M , et al . MAPK3/1 (ERK1/2) in ovarian granulosa cells are essential for female fertility [J]. Science , 2009 , 324 ( 5929 ): 938 - 941 .

XU P , ZHANG G , HOU S , et al . MAPK8 mediates resistance to temozolomide and apoptosis of glioblastoma cells through MAPK signaling pathway [J]. Biomed Pharmacother , 2018 , doi： 10.1016/j.biopha.2018. 06.084 http://dx.doi.org/10.1016/j.biopha.2018.06.084 .

NAKATANI Y , AMANO T , YAMAMOTO H , et al . Yokukansan enhances the proliferation of B65 neuroblastoma [J]. J Tradit Complement Med , 2017 , 7 ( 1 ): 34 - 44 .

BRASTIANOS P K , HOROWITZ P M , SANTAGATA S , et al . Genomic sequencing of meningiomas identifies oncogenic SMO and Akt1 mutations [J]. Nat Genet , 2013 , 45 ( 3 ): 285 - 289 .

YANG C , SUN N , REN Y , et al . Association between Akt1 gene polymorphisms and depressive symptoms in the Chinese Han population with major depressive disorder [J]. Neural Regen Res , 2012 , 7 ( 3 ): 235 - 239 .

NIRAULA A , WITCHER K G , SHERIDAN J F , et al . Interleukin-6 induced by social stress promotes a unique transcriptional signature in the monocytes that facilitate anxiety [J]. Biol Psychiatry , 2019 , 85 ( 8 ): 679 - 689 .

VIEIRA F , BACHION M M , COELLO A S , et al . The use of NANDA's Taxonomy Ⅱ for assessing puerperal anxiety within a community [J]. Revista Gaucha de Enfermagem , 2010 , 31 ( 3 ): 544 - 551 .

VOLLERT C , ZAGAAR M , HOVATTA I , et al . Exercise prevents sleep deprivation-associated anxiety-like behavior in rats: potential role of oxidative stress mechanisms [J]. Behav Brain Res , 2011 , 224 ( 2 ): 233 - 240 .

浏览量

下载量

CSCD

文章被引用时，请邮件提醒。

提交

工具集

关联资源

基于血清代谢组学探讨安寐丹“生熟酸枣仁”同用及拆方改善失眠大鼠焦虑与认知障碍的差异及机制

基于UPLC-Q-TOF-MS结合网络药理学探讨黑逍遥散改善失眠大鼠学习记忆能力的药效物质基础及作用机制

复方狼毒酊干预湿毒蕴结型多发性掌跖疣的临床疗效及机制探讨