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  

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

作　　者：木克达斯·阿布都热合曼 郭振杨 葛均波 李华 ABDURAHMAN Mukaddas;GUO Zhenyang;GE Junbo;LI Hua(Department of Cardiology,Zhongshan Hospital,Fudan University,Shanghai 200032,China)

机构地区：[1]复旦大学附属中山医院心内科,上海200032

出　　处：《中国临床医学》2025年第1期46-57,共12页Chinese Journal of Clinical Medicine

基　　金：国家自然科学基金(82170334).

摘　　要：目的探讨银杏叶提取物(Ginkgo biloba extract,GBE)对氧糖剥夺/复氧(oxygen and glucose deprivation/reperfusion,OGD/R)条件下心脏微血管内皮细胞(cardiac microvascular endothelial cells,CMECs)的作用及其分子机制。方法建立OGD/R诱导的CMECs损伤模型,根据不同处理分为4组:常氧空白对照组(WT组)、WT+GBE组、OGD/R组和OGD/R+GBE组。采用流式细胞术检测各组细胞凋亡水平,MitoSox染色检测细胞氧化应激水平,划痕实验检测细胞迁移能力,Western印迹法检测PERK/eIF2α/CHOP、核转录因子κB(nuclear factor kappa B,NF-κB)及内皮细胞功能相关蛋白标志物的表达水平。结果与WT组相比,OGD/R组的内皮细胞凋亡水平显著上升,细胞功能损伤明显加重,p-NF-κB、血管细胞黏附分子1(vascular cell adhesion molecule-1,VCAM-1)、细胞间黏附分子1(intercellular cell adhesion molecule-1,ICAM-1)蛋白表达显著上调(P<0.05),CHOP信号通路激活明显增强(P<0.05);经GBE干预后,受损内皮细胞的凋亡明显减少,氧化应激和炎症水平明显下调,p-NF-κB蛋白表达显著减少(P<0.05),CHOP信号通路明显抑制(P<0.05)。进一步分析发现,GBE通过促进SIRT6表达来调控上述分子,进而减轻OGD/R条件下CMECs损伤;敲低SIRT6后,GBE减轻损伤的程度明显下降。结论GBE通过促进SIRT6蛋白表达来调控NF-κB炎症分子及CHOP信号通路,改善OGD/R损伤造成的内皮细胞功能障碍、内质网应激和内皮细胞凋亡。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.

关 键 词：银杏叶提取物 心脏微血管内皮细胞 氧糖剥夺/复氧 内质网应激 SIRT6 

分 类 号：R54[医药卫生—心血管疾病]