Brain Material Basis and Relevant Mechanism of Acute Stroke Treated with Rhei Radix et Rhizoma Based on Homotherapy for Heteropathy Using Proteomics

Tao LIU; Yang WANG; Han-jin CUI; Tao TANG

doi:10.13422/j.cnki.syfjx.20201923

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Brain Material Basis and Relevant Mechanism of Acute Stroke Treated with Rhei Radix et Rhizoma Based on Homotherapy for Heteropathy Using Proteomics

Pharmacology | 更新时间：2020-09-16

- Brain Material Basis and Relevant Mechanism of Acute Stroke Treated with Rhei Radix et Rhizoma Based on Homotherapy for Heteropathy Using Proteomics
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 26, Issue 19, Pages: 160-168(2020)
- 作者机构：
  
  1.新疆医科大学附属中医医院，乌鲁木齐 830000
  2.中南大学湘雅医院，长沙 410008
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20201923
  CLC： R22;R242;R2-031;R285.5
- Received：21 January 2020，
  
  Published Online：27 July 2020，
  
  Published：05 October 2020
- 稿件说明：
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刘涛,王杨,崔寒尽等.基于蛋白质组学大黄异病同治急性中风大鼠脑物质的基础及相关机制[J].中国实验方剂学杂志,2020,26(19):160-168.

LIU Tao,WANG Yang,CUI Han-jin,et al.Brain Material Basis and Relevant Mechanism of Acute Stroke Treated with Rhei Radix et Rhizoma Based on Homotherapy for Heteropathy Using Proteomics[J].Chinese Journal of Experimental Traditional Medical Formulae,2020,26(19):160-168.
刘涛,王杨,崔寒尽等.基于蛋白质组学大黄异病同治急性中风大鼠脑物质的基础及相关机制[J].中国实验方剂学杂志,2020,26(19):160-168. DOI： 10.13422/j.cnki.syfjx.20201923.

LIU Tao,WANG Yang,CUI Han-jin,et al.Brain Material Basis and Relevant Mechanism of Acute Stroke Treated with Rhei Radix et Rhizoma Based on Homotherapy for Heteropathy Using Proteomics[J].Chinese Journal of Experimental Traditional Medical Formulae,2020,26(19):160-168. DOI： 10.13422/j.cnki.syfjx.20201923.

摘要

目的

基于定量蛋白质组学和生物信息学分析，探索大黄异病同治急性中风的物质基础及机制。

方法

采用线栓法制备缺血再灌注的缺血性中风（IS）大鼠模型和胶原酶来诱导的出血性中风（ICH）模型。将60只SD大鼠随机分为缺血性中风假手术组（Sham1）

缺血性中风组（IS）

出血性中风+大黄治疗组（DH1）

出血性中风假手术组（Sham2）

出血性中风（ICH）组和出血性中风+大黄治疗组（DH2），每组10只。IS，Sham1和DH1组在24 h后，ICH，Sham2和DH2组在48 h后，生理盐水灌注后取脑组织行定量蛋白质组学分析，鉴定差异表达蛋白（DEPs）。对共性DEPs进行生物信息学分析，并对相关的DEPs进行蛋白免疫印迹验证。

结果

大黄调节急性中风疾病相关共性DEPs 21个（上调12个，下调9个）。京都基因和基因组百科全书（KEGG）分析显示，富集了肌萎缩侧索硬化症（ALS）通路，通路中包含神经丝蛋白轻链多肽（Nefl），神经丝蛋白中链多肽（Nefm），神经丝蛋白重链多肽（Nefh）。大黄异病同治急性中风共性机制主要包括能量代谢、离子稳态、突触相关蛋白的调节、细胞周期及神经形成。共性DEPs验证，大黄治疗后，GTP结合蛋白REM2（Rem2），酪氨酸3-单加氧酶（Th），Nefl和神经调制蛋白（Gap43）表达量与相应模型组比较差异均有统计学意义（

0.05）。其中，治疗后Nefl表达为下调，而Rem2，Th和Gap43表达为上调，此结果与蛋白质组学检测结果一致。

结论

该研究建立了大黄-异病同治-差异蛋白质表达谱，能量代谢、离子稳态、突触相关蛋白调节、细胞周期及神经形成是其共性机制。

Abstract

Objective

To explore the material basis and mechanism of acute stroke treated with Rhei Radix et Rhizoma based on Homotherapy for Heteropathy using the analysis of proteomics and bioinformatics.

Method

A total of 60 male Sprague-Dawley（SD）rats were randomly divided into ischemic stroke（IS） sham-operation group (Sham1)

IS model group (IS)

IS+ Rhei Radix et Rhizoma treatment group (DH1)，ICH sham-operation group (Sham2)

intracerebral hemorrhage（ICH） model group (ICH)

and ICH + Rhei Radix et Rhizoma treatment group (DH2)

with 10 rats in each group. After cerebral perfusion

the brain tissues were quantified by proteomic analysis

and differentially expressed proteins (DEPs) were identified. Specimens of IS

Sham1

and DH1 groups were collected at 24 hours

while those of ICH

Sham2

and DH2 groups were collected at 48 hours. The common DEPs were analyzed by bioinformatics

and the relevant DEPs were verified by Western blot.

Result

Rhei Radix et Rhizoma regulated 21 common DEPs associated with acute stroke (including 12 up-regulated and 9 down-regulated). According to Kyoto Encyclopedia of Genes and Genomes（KEGG） analysis

amyotrophic lateral sclerosis (ALS) pathway was enriched

and three proteins [Neurofilament light polypeptide (Nefl)

Neurofilament medium polypeptide (Nefm)

Neurofilament heavy polypeptide (Nefh)] involved in this pathway. Energy metabolism

ion homeostasis

regulation of synaptophysin

cell cycle and neurogenesis were the common mechanisms of "Homotherapy for Heteropathy". After treatment with Rhei Radix et Rhizoma

the expression levels of GTP binding protein REM2 (Rem2)

tyrosine 3-monooxygena (Th)

Nefl and neuromodulin (Gap43) were significantly higher than those of the corresponding model group (

0.05). The expression of Nefl was down-regulated

while the expressions of Rem2，Th and Gap43 were up-regulated

which was consistent with the results of proteomics.

Conclusion

Rhei Radix et Rhizoma-homotherapy-differential protein expression profile is established is study. Energy metabolism

ion homeostasis

regulation of synaptophysin

cell cycle and neurogenesis are the common mechanisms.

关键词

Keywords

references

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