[1]张莉,王露,肖涵,等.抑制Fyn可激活Nrf2信号通路减轻大鼠脑出血后氧化应激损伤[J].第三军医大学学报,2019,41(21):2035-2042.
 ZHANG Li,WANG Lu,XIAO Han,et al.Inhibition of Fyn activates Nrf2 signaling pathway to attenuate oxidative stress injury after intracerebral hemorrhage in rats[J].J Third Mil Med Univ,2019,41(21):2035-2042.
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《第三军医大学学报》[ISSN:1000-5404/CN:51-1095/R]

卷:
41卷
期数:
2019年第21期
页码:
2035-2042
栏目:
基础医学
出版日期:
2019-11-15

文章信息/Info

Title:
Inhibition of Fyn activates Nrf2 signaling pathway to attenuate oxidative stress injury after intracerebral hemorrhage in rats
作者:
张莉王露肖涵甘荟陈辉郑淑月翟瑄赵敬梁平
1400016 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1,基础医学院病理生理学教研室
Author(s):
ZHANG Li WANG Lu XIAO Han GAN Hui CHEN Hui ZHENG Shuyue ZHAI Xuan ZHAO Jing LIANG Ping

Department of Neurosurgery, Key Laboratory of Child Development and Disorders of Ministry of Education, National Clinical Research Center for Child Health and Disorders (Chongqing), China International Science and Technology Cooperation Base of Child Development and Critical Disorders,Chongqing Key Laboratory of Pediatrics, Children’s Hospital of Chongqing Medical University, Chongqing, 400016; Department of Pathophysiology, College of Basic Medical Sciences, Chongqing Medical University, Chongqing, 400016, China

关键词:
脑出血Fyn核因子E2相关因子2氧化应激HO-1
Keywords:
intracerebral hemorrhage Fyn nuclear factor erythroid 2-related factor 2 oxidative stress heme oxygenase-1
分类号:
R345; R363.22; R743.34
文献标志码:
A
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、H2O2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(P<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(P<0.05),血脑屏障通透性降低;脑组织SOD、GSH、GSH-PX活力减少(P<0.05),而MDA、H2O2含量增加(P<0.05);脑组织中Nrf2、HO-1、NQO1的表达增高(P<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(P<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(P<0.05),而MDA、 H2O2含量减低(P<0.05);脑组织中Nrf2、HO-1、NQO1的表达增加(P<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:

ObjectiveTo investigate the effect of tyrosine kinase Fyn on oxidative stress after intracerebral hemorrhage (ICH) in rats and its potential mechanism. MethodsA 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 H2O2 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. ResultsCompared with the Sham group, the ICH group had increased expression of Fyn in brain tissue (P<0.05), elevated mortality, increased neuronal degeneration and necrosis, decreased modified Garcia score (P<0.05), elevated score of balance beam test (P<0.05), decreased blood-brain barrier permeability, inhibited activities of brain tissue SOD, GSH and GSH-PX (P<0.05), increased contents of MDA and H2O2 (P<0.05), and enhanced expression levels of Nrf2, HO-1 and NQO1 (P<0.05). There were 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 (P<0.05), and decreased blood-brain barrier permeability. The activities of SOD, GSH and GSH-PX of the brain tissue around hematoma were enhanced (P<0.05), while the contents of MDA and H2O2 were decreased (P<0.05) and the expression of Nrf2, HO-1 and NQO1 were up-regulated (P<0.05). ConclusionInhibition of Fyn attenuates oxidative stress injury after cerebral hemorrhage in rats, and its mechanism may be related to activation of Nrf2 signaling pathway.

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更新日期/Last Update: 2019-11-12