心脑血管病防治2025，Vol.25Issue(11)：3-9,后插1,8.DOI:10.3969/j.issn.1009-816x.2025.11.002
基于NF-κB/COX-2信号通路探讨S1P对血管内皮细胞炎症反应及凋亡的作用机制
Mechanism of sphingosine-1-phosphate in the inflammation and apoptosis of vascular endothelial cells via nuclear factor-κB/cyclooxygenase-2 signaling pathway
摘要
Abstract
Objective To explore the effect of sphingosine-1-phosphate(S1P)on inflammation and apoptosis in vascular endothelial cells and its relationship with the nuclear factor-κB(NF-κB)/cyclooxygenase-2(COX-2)signaling pathway.Methods Mouse aortic endothelial cells were cultured in vitro and divided into 6 groups.Control group:no cell damage inducer was added.The remaining 5 groups were all treated with ox-LDL to induce cellular injury,including Model group,NC-siRNA group(transfected with NC-siRNA),sphingosine-1-phosphate receptor 2(S1PR2)-siRNA group(transfected with S1PR2-siRNA),TNF-α group(treated with 10 ng/mL TNF-α),TNF-α+S1PR2-siRNA group(transfected with S1PR2-siRNA and then treated with 10 ng/mL TNF-α).Cell viability was detected by CCK-8 assay.Apoptosis rate was measured by flow cytometry.The mRNA expression levels of S1PR2,intercellular adhesion molecule-1(ICAM-1),vascular cell adhesion molecule-1(VCAM-1),interleukin-6(IL-6),and interleukin-10(IL-10)were detected by qRT-PCR.The protein expression levels of S1PR2,NF-κB,phosphorylation NF-κB(p-NF-κB),COX-2,B-cell lymphoma-2(Bcl-2),and B-cell-lymphoma-2 associated X protein(Bax)were determined by western blot.Results Significant differences were observed among the six groups in terms of cell viability,apoptosis rate,and the expression levels of S1PR2(both mRNA and protein),the mRNA expression levels of endothelial inflammatory cytokines(ICAM-1,VCAM-1,IL-6,IL-10),the protein expression levels of Bax and Bcl-2,as well as the ratios of p-NF-κB to NF-κB and COX-2(F=187.934,84.260,127.339,20.708,120.366,63.403,183.976,98.418,130.398,64.454,125.520,65.845,respectively;P<0.05).Compared with the Control group,the Model group exhibited decreased cell viability and an increased apoptosis rate;upregulated expression levels of S1PR2(both mRNA and protein),ICAM-1,VCAM-1,IL-6,Bax,COX-2,and the p-NF-κB/NF-κB ratio;downregulated expressions of IL-10 and Bcl-2,all these differences were statistically significant(P<0.05).Compared with the Model group,the S1PR2-siRNA group showed increased cell viability,decreased apoptosis rate,downregulation of expressions of S1PR2(both mRNA and protein),ICAM-1,VCAM-1,IL-6,Bax,COX-2,and the p-NF-κB/NF-κB ratio,and upregulation of expressions of IL-10 and Bcl-2,all these differences were statistically significant(P<0.05).Compared with the Model group,the TNF-α group demonstrated significantly decreased cell viability,increased apoptosis rate,upregulated expression levels of S1PR2,ICAM-1,VCAM-1,IL-6,Bax,COX-2,and the p-NF-κB/NF-κB ratio;and downregulated expressions of IL-10 and Bcl-2(P<0.05).Compared with the S1PR2-siRNA group,the TNF-α+S1PR2-siRNA group showed significantly decreased cell viability,increased apoptosis rate,upregulation of expression levels of S1PR2(both mRNA and protein),ICAM-1,VCAM-1,IL-6,Bax,COX-2,and the p-NF-κB/NF-κB ratio,and downregulation of expressions of IL-10 and Bcl-2,all these differences were statistically significant(P<0.05).Compared with the TNF-α group,the TNF-α+S1PR2-siRNA group exhibited significantly increased cell viability,decreased apoptosis rate,downregulation of expression levels of S1PR2(both mRNA and protein),ICAM-1,VCAM-1,IL-6,Bax,COX-2,and the p-NF-κB/NF-κB ratio,and upregulation of expressions of IL-10 and Bcl-2,all these differences were statistically significant(P<0.05).Conclusion S1PR2 regulates the inflammation and apoptosis in vascular endothelial cells by regulating the NF-κB/COX-2 signaling pathway.关键词
血管内皮细胞/1-磷酸鞘氨醇/1-磷酸鞘氨醇受体2/炎症反应/细胞凋亡/核因子-κB/环氧合酶2信号通路Key words
Vascular endothelial cells/Sphingosine-1-phosphate/Sphingosine-1-phosphate receptor 2/Inflammation/Apoptosis/Nuclear factor-κB/cyclooxygenase-2 signaling pathway引用本文复制引用
阴艳萍,张央,江建军,许莎莎..基于NF-κB/COX-2信号通路探讨S1P对血管内皮细胞炎症反应及凋亡的作用机制[J].心脑血管病防治,2025,25(11):3-9,后插1,8.基金项目
台州市科技计划项目(21ywa02) （21ywa02）
