Dexmedetomidine alleviates ferroptosis in rat cerebral ischemia/re-perfusion injury by inhibiting the Nrf2 pathway
10.12092/j.issn.1009-2501.2025.07.006
- VernacularTitle:右美托咪定抑制Nrf2通路减轻大鼠脑缺血/再灌注损伤铁死亡
- Author:
Huanran YANG
1
;
Shengnan WU
;
Qin GAO
Author Information
1. 蚌埠医科大学口腔医学院
- Publication Type:Journal Article
- Keywords:
cerebral ischemia and reperfusion in-jury;
dexmedetomidine;
nuclear factor erythroid derived 2-like 2 pathway;
hippocampal neurons;
ox-idative stress
- From:
Chinese Journal of Clinical Pharmacology and Therapeutics
2025;30(7):921-928
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To observe the effect of dexme-detomidine(DEX)on cerebral ischemia and reperfu-sion(I/R)injury and investigate the possible mecha-nism of nuclear factor erythroid derived 2-like 2(Nrf2)mediated ferroptosis on hippocampal neu-rons.METHODS:The oxygen glucose deprivation/reoxygenation(OGD/R)model in rat primary cul-tured hippocampal neurons was simulated,DEX(50 μmol/L)and Nrf inhibitor BRU(100 nmol/L)were used to observe the changes of ROS levels by DHE fluorescence probe.The middle cerebral ar-tery occlusion model in male SD rats were estab-lished,the degree of neurological impairment was detected by Longa score,and cerebral infarct size was detected by TTC staining.The Fe2+concentra-tion and levels of oxidative stress related factors were detected,oxidative stress and ferroptosis re-lated protein expressions were detected by West-ern blot.RESULTS:The fluorescence intensity of DHE in OGD/R+Dex Group was lower than that in CON group,and the fluorescence intensity of DHE in OGD/R+DEX+BRU group was higher than that in OGD/R+Dex group.Compared with Sham group,the Longa score and cerebral infarct size in I/R group were significantly increased(P＜0.01),the lev-els of SOD,CAT,GSH and GSH-PX were significantly decreased.MDA and Fe2+concentrations were in-creased,the protein expressions of Nrf2,HO-1,GPX4,FTH1 and FPN1 were decreased,and TFR1 protein expression was increased.Compared with I/R group,in DEX+I/R group,the Longa score and ce-rebral infarct size were decreased(P＜0.01),the lev-els of SOD,CAT,GSH and GSH-PX were increased.MDA and Fe2+concentrations were decreased,the protein expressions of Nrf2,HO-1,GPX4,FTH1 and FPN1 were increased,and TFR1 protein expression was decreased.The Nrf2 inhibitor Bru reversed the role of DEX.CONCLUSION:DEX protects against ce-rebral I/R injury through activating Nrf2 signaling pathway and inhibiting ferroptosis in hippocampal neurons.
