Ginkgo biloba extract alleviates oxygen and glucose deprivation/reperfusion injury in cardiac microvascular endothelial cells by regulating NF-κB and CHOP signaling pathways through SIRT6
10.12025/j.issn.1008-6358.2025.20241262
- VernacularTitle:银杏叶提取物通过SIRT6调控NF-κB和CHOP信号通路改善氧糖剥夺/复氧诱导的心脏微血管内皮细胞损伤
- Author:
Mukaddas ABDURAHMAN
1
;
Zhenyang GUO
1
;
Junbo GE
1
;
Hua LI
1
Author Information
1. 复旦大学附属中山医院心内科,上海 200032
- Publication Type:Journal Article
- Keywords:
Ginkgo biloba extract;
cardiac microvascular endothelial cells;
oxygen and glucose deprivation/reperfusion;
endoplasmic reticulum stress;
SIRT6
- From:
Chinese Journal of Clinical Medicine
2025;32(1):46-57
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the effects of Ginkgo biloba extract(GBE)on cardiac microvascular endothelial cells(CMECs)under oxygen and glucose deprivation/reperfusion(OGD/R)condition and its molecular mechanisms.Methods An OGD/R-induced injury model was established in CMECs.According to different intervention,CMECs were divided into four groups:normoxia blank control group(WT group),WT+GBE group,OGD/R group,and OGD/R+GBE group.Cell apoptosis was detected by flow cytometry technology in each group.The oxidative stress was examined by MitoSox staining.The migration abilities were measured by scratch assay.The expressions of PERK/eIF2α/CHOP,nuclear factor kappa B(NF-κB),and endothelial cell function markers were detected by Western blotting.Results Compared with the WT group,the endothelial cell apoptosis level in the OGD/R group significantly increased,with markedly aggravated cellular dysfunction.The expressions of p-NF-κB,vascular cell adhesion molecule-1(VCAM-1),and intercellular cell adhesion molecule-1(ICAM-1)were significantly upregulated(P<0.05),and the activation of the CHOP signaling pathway was notably enhanced(P<0.05).After intervention with GBE,endothelial cell apoptosis caused by OGD/R injury was significantly reduced,oxidative stress and inflammation levels were markedly downregulated,and the expression of p-NF-κB was considerably decreased(P<0.05),while the CHOP signaling pathway was notably inhibited(P<0.05).Furthermore,it was found that GBE could promote expression of SIRT6 to regulate the above molecules,thereby alleviating cardiac microvascular endothelial cell injury under OGD/R condition.On the contrary,when SIRT6 was knocked down,the protective effects were significantly reduced.Conclusions GBE improves endothelial cell dysfunction,endoplasmic reticulum stress,and endothelial cell apoptosis caused by OGD/R injury by promoting the expression of SIRT6 protein,thus regulating the NF-κB inflammatory pathway and CHOP signaling pathway.