Mechanism of Guhong Injection Against Cerebral Ischemia Based on Transcriptome Analysis

Rui ZHOU; Chang-pei XIANG; Jin-huan GAO; Yi ZHANG; Jing-jing ZHANG; Hong-jun YANG

doi:10.13422/j.cnki.syfjx.20200505

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Mechanism of Guhong Injection Against Cerebral Ischemia Based on Transcriptome Analysis

Data Mining | 更新时间：2021-02-09

- Mechanism of Guhong Injection Against Cerebral Ischemia Based on Transcriptome Analysis
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 26, Issue 7, Pages: 195-203(2020)
- 作者机构：
  
  1.云南中医药大学，昆明　 650500
  2.中国中医科学院　中药研究所，北京　 100700
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20200505
  CLC： R2-0; R22; R285.5; R289
- Received：25 July 2019，
  
  Published Online：19 November 2019，
  
  Published：05 April 2020
- 稿件说明：
移动端阅览
Rui ZHOU, Chang-pei XIANG, Jin-huan GAO, et al. Mechanism of Guhong Injection Against Cerebral Ischemia Based on Transcriptome Analysis[J]. Chinese journal of experimental traditional medical formulae, 2020, 26(7): 195-203.
DOI：

Rui ZHOU, Chang-pei XIANG, Jin-huan GAO, et al. Mechanism of Guhong Injection Against Cerebral Ischemia Based on Transcriptome Analysis[J]. Chinese journal of experimental traditional medical formulae, 2020, 26(7): 195-203. DOI： 10.13422/j.cnki.syfjx.20200505.

摘要

目的：

在确定谷红注射液保护脑缺血的基础上，采用RNA-Seq转录组测序与生物信息分析的方法探究谷红注射液抗脑缺血的分子机制。

方法：

采用线栓法制备大脑中动脉栓塞(MCAO)模型，设置假手术组，模型组，谷红注射液低、中剂量组(0.625，2.5 mL·kg

-1

·d

-1

)，阳性药组(金纳多注射液，8 mL·kg

-1

·d

-1

)，通过Ludmila Belayev 12分评分法进行药效学评价，并采用RNA-Seq技术检测药物干预前后的差异基因，使用DAVID，String及The Human Phenotype Ontology等数据库，进行富集分析、聚类分析、以及与脑缺血疾病靶标的关联分析，通过Cytoscape3.4.0构建相关的调控网络。

结果：

与假手术组相比，模型组大鼠可见明显神经功能缺损(

0.01)；与模型组比较，谷红注射液高剂量组减轻了大鼠神经功能损伤(

0.05)。转录组数据分析表明谷红注射液主要是通过调控细胞凋亡，炎症反应，氧化应激，Toll样受体信号通路及丝裂原激活的蛋白激酶(MAPK)信号通路等生物学过程干预脑缺血。此外，谷红液射液干预脑缺血的差异基因关联到20个脑缺血疾病相关的靶标，且关联到64个MAPK信号通路相关的基因，其中23个基因参与凋亡与炎症等过程。

结论：

谷红注射液通过多条途径发挥抗脑缺血作用，其中MAPK信号通路是其发挥抗凋亡及炎症作用的重要途径。

Abstract

Objective:

Based on the protective effect of Guhong injection (GH) on cerebral ischemia

mechanism of GH against cerebral ischemia was identified using RNA-seq transcriptome and bioinformation analysis.

Method:

The model of middle cerebral artery occlusion (MCAO) was established through thread embolization. Sham group

model group

low-dose GH group (0.625 mL·kg

-1

·d

-1

)

high-dose GH group (2.5 mL·kg

-1

·d

-1

)

positive group (Ginaton

8 mL·kg

-1

·d

-1

) were set up. Ludmila Belayev 12-point scoring method was applied to assess the protective effect of GH against MCAO-induced cerebral ischemia. And the differentially expressed genes after treatment with GH were identified by RNA-Seq technology. Enrichment analysis

cluster analysis and association analysis on disease targets of cerebral ischemia were carried out through such databases as DAVID

String and The Human Phenotype Ontology. Finally

the regulatory network was constructed by Cytoscape3.4.0.

Result:

Compared with the sham group

the neurological impairment was obvious in the model group (

0.01)

and the neurological impairment was alleviated in the GH group compared with the model group (

0.05). RNA-Seq technology analysis showed that GH regulated genes involving such biological processes as cell apoptosis

inflammation

oxidative stress

toll-like signaling pathway and mitogen-activated protein kinase (MAPK) signaling pathway. Twenty disease targets and 64 MAPK signaling pathway genes were associated with differentially expressed genes after GH treatment

in which 23 genes were involved in apoptosis and inflammation.

Conclusion:

GH protected against cerebral ischemia in many ways

among which MAPK signaling pathway is an important way to exert its effect in inhibiting apoptosis and inflammation.

关键词

Keywords

references

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