Di-san junyi daxue xuebao (Nov 2019)

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

  • ZHANG Li,
  • WANG Lu,
  • XIAO Han,
  • GAN Hui,
  • CHEN Hu

DOI
https://doi.org/10.16016/j.1000-5404.201906063
Journal volume & issue
Vol. 41, no. 21
pp. 2035 – 2042

Abstract

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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 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. Results Compared 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). 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.

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