Inhibition of Fyn activates Nrf2 signaling pathway to attenuate oxidative stress injury after intracerebral hemorrhage in rats

Li ZHANG; Lu WANG; Han XIAO; Hui GAN; Hui CHEN; Shuyue ZHENG; Xuan ZHAI; Jing ZHAO; Ping LIANG

doi:10.16016/j.1000-5404.201906063

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Inhibition of Fyn activates Nrf2 signaling pathway to attenuate oxidative stress injury after intracerebral hemorrhage in rats

Basic Medicine | 更新时间：2026-01-09

- Inhibition of Fyn activates Nrf2 signaling pathway to attenuate oxidative stress injury after intracerebral hemorrhage in rats
- Journal of Third Military Medical University Issue 21, Pages: 2035-2042(2019)
- 作者机构：
  
  1.400016 重庆，重庆医科大学:儿童发育疾病研究教育部重点实验室，国家儿童健康与疾病临床医学研究中心(重庆)，儿童发育重大疾病国家国际科技合作基地，儿科学重庆市重点实验室
  2.基础医学院病理生理学教研室
- 作者简介：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(81671158);the Key Project of Chongqing Municipal Health and Family Planning Commission(2015ZDXM016);the Key Project of Basic Science and Frontier Technology Research of Chongqing Science and Technology Commission(CSTC2015jcyjBX0144)
- DOI：10.16016/j.1000-5404.201906063
  CLC： R345;R363.22;R743.34
- Received：11 June 2019，
  
  Revised：2019-07-11，
  
  Published：15 November 2019
- 稿件说明：
移动端阅览
Li ZHANG, Lu WANG, Han XIAO, et al. Inhibition of Fyn activates Nrf2 signaling pathway to attenuate oxidative stress injury after intracerebral hemorrhage in rats[J]. Journal of Third Military Medical University, 2019, (21): 2035-2042.
DOI：

Li ZHANG, Lu WANG, Han XIAO, et al. Inhibition of Fyn activates Nrf2 signaling pathway to attenuate oxidative stress injury after intracerebral hemorrhage in rats[J]. Journal of Third Military Medical University, 2019, (21): 2035-2042. DOI： 10.16016/j.1000-5404.201906063.

摘要

目的

探讨抑制酪氨酸激酶Fyn(tyrosine kinase Fyn)对大鼠脑出血(intracerebral hemorrhage，ICH)后氧化应激的影响及其潜在机制。

方法

96只雄性SD大鼠采用随机数字表法分为4组:假手术组(Sham组)、脑出血组(ICH组)、阴性对照组(ICH+Si-NC组)和Fyn敲低组(ICH+Si-Fyn组)。基底节注入50 μL自体血建立ICH模型，侧脑室注射小干扰片段抑制Fyn的表达，ICH后24 h进行病死率统计、尼氏染色、神经功能评分、血脑屏障通透性检测，ELASA检测ICH大鼠血肿周围脑组织的SOD、GSH、GSH-PX、MDA、H

含量，Western blot检测脑组织中Fyn、核因子E2相关因子2(factor erythroid 2-related factor 2

Nrf2)及Nrf2下游血红素加氧酶-1(heme oxygenase-1

HO-1)和醌氧化还原酶1(quinine oxidoreductase 1

NQO1)的表达。

结果

与Sham组相比，ICH组脑组织中Fyn的表达增高(

0.05)，大鼠病死率增高、神经元变性坏死增多、改良Garcia评分减低、平衡木实验评分增加(

0.05)，血脑屏障通透性降低；脑组织SOD、GSH、GSH-PX活力减少(

0.05)，而MDA、H

含量增加(

0.05)；脑组织中Nrf2、HO-1、NQO1的表达增高(

0.05)。ICH组与ICH+Si-NC组无明显差异。与ICH+Si-NC组相比，siRNA-Fyn可有效抑制Fyn的表达，ICH+Si-Fyn组大鼠病死率降低、神经元变性坏死减少、神经功能评分改善(

0.05)，血脑屏障通透性降低；脑组织血肿周围SOD、GSH、GSH-PX活力增加(

0.05)，而MDA、H

含量减低(

0.05)；脑组织中Nrf2、HO-1、NQO1的表达增加(

0.05)。

结论

抑制Fyn可减轻大鼠脑出血后氧化应激损伤，其机制可能与激活Nrf2信号通路有关。

Abstract

Objective

To investigate the effect of tyrosine kinase Fyn on oxidative stress after intracerebral hemorrhage (ICH) in rats and its potential mechanism.

Methods

A total of 96 male SD rats were randomly assigned to 4 groups

that is

Sham group

ICH group

negative control group (ICH+Si-NC group) and Fyn knockdown group (ICH+Si-Fyn) group. ICH model was induced

via

injecting 50 μL autologous blood into the basal ganglia. Small interfering fragments were injected into the lateral ventricle to inhibit the expression of Fyn. Mortality

Nissl staining

neurological function score

blood-brain barrier permeability test were detected at 24 h after ICH

and ELASA was used to detect the contents of SOD

GSH

GSH-PX

MDA

and H

in the brain tissue of ICH rats. The expression of Fyn

nuclear factor erythroid 2-related factor 2 (Nrf2) and Nrf2 downstream proteins

heme oxygenase-1 (HO-1) and quinine oxidoreductase 1 (NQO1) were detected by Western blotting.

Results

Compared with the Sham group

the ICH group had increased expression of Fyn in brain tissue (

0.05)

elevated mortality

increased neuronal degeneration and necrosis

decreased modified Garcia score (

0.05)

elevated score of balance beam test (

0.05)

decreased blood-brain barrier permeability

inhibited activities of brain tissue SOD

GSH and GSH-PX (

0.05)

increased contents of MDA and H

(

0.05)

and enhanced expression levels of Nrf2

HO-1 and NQO1 (

0.05). There we

re no significant differences in above indicators between the ICH group and the ICH+Si-NC group. Compared with the ICH+Si-NC group

Si-Fyn transfection effectively inhibited the expression of Fyn

decreased the mortality of the ICH+Si-Fyn group

attenuated neuronal degeneration and necrosis

improved neurological function score (

0.05)

and decreased blood-brain barrier permeability. The activities of SOD

GSH and GSH-PX of the brain tissue around hematoma were enhanced (

0.05)

while the contents of MDA and H

were decreased (

0.05) and the expression of Nrf2

HO-1 and NQO1 were up-regulated (

0.05).

Conclusion

Inhibition of Fyn attenuates oxidative stress injury after cerebral hemorrhage in rats

and its mechanism may be related to activation of Nrf2 signaling pathway.

关键词

Keywords

references

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