Mechanism of glycogen synthase kinase-3β participating in stroke-induced inflammatory brain injury by regulating endoplasmic reticulum-mitochondria coupling
10.19845/j.cnki.zfysjjbzz.2025.0122
- VernacularTitle:脑卒中GSK-3β调控内质网-线粒体偶联参与炎症性脑损伤的机制研究
- Author:
Jianhua LEI
1
;
Hefang DU
2
;
Yuxiao LIU
2
Author Information
1. 邯郸市中心医院神经内科，河北 邯郸 056000
2. 华北医疗健康集团邢台总医院骨六科，河北 邢台 054000
- Publication Type:Journal Article
- Keywords:
Stroke;
Glycogen synthase kinase-3β;
Endoplasmic reticulum-mitochondria coupling;
Brain injury
- MeSH:
Stroke
- From:
Journal of Apoplexy and Nervous Diseases
2025;42(7):637-640
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the mechanism of glycogen synthase kinase-3β（GSK-3β） participating in stroke-induced inflammatory brain injury through endoplasmic reticulum-mitochondria coupling， and to provide a theoretical reference and potential targets for precise treatment. Methods A rat model of middle cerebral artery occlusion was established， and the rats were divided into sham-operation group， model group， and GSK-3β inhibitor（TDZD-8） intervention group. Neurological function score was used to evaluate the degree of brain injury； TTC staining was used to evaluate cerebral infarct area； electron microscopy was used to observe mitochondrial ultrastructure； mitochondrial calcium concentration was measured； ELISA was used to measure the levels of inflammatory factors[tumor necrosis factor-α（TNF-α）and interleukin-1β（IL-1β）]， and Western blot was used to measure the expression levels of related proteins. Results Compared with the sham-operation group， the model group had significant neurological function impairment， an increase in cerebral infarct area， and significant increases in the expression levels of inflammatory factors and GSK-3β，with enhanced endoplasmic reticulum-mitochondria coupling and mitochondrial calcium overload. TDZD-8 significantly improved the above indicators and reduced the levels of inflammatory factors and cerebral infarct area. Conclusion Abnormal activation of GSK-3β damages brain tissue by regulating endoplasmic reticulum-mitochondria coupling and promotes mitochondrial calcium overload and inflammatory response. Inhibiting GSK-3β activity can effectively improve stroke-induced inflammatory brain injury， which provides a new pathway and a molecular target for developing precise treatment strategies.
- Full text:2025081115592867082脑卒中GSK-3β调控内质网-线粒体偶联参与炎症性脑损伤的机制研究.pdf
