烟台大学学报（自然科学与工程版）2025，Vol.38Issue(3)：314-324,11.DOI:10.13951/j.cnki.37-1213/n.240312
荷叶碱逆转油酸诱导的血管内皮细胞衰老
Nuciferine Reversed Senescence Induced by Oleic Acid in Vascular Endothelial Cells
摘要
Abstract
In order to explore the molecular mechanism and the intervention effect of nuciferine on the senescence induced by oleic acid(OA)in vascular endothelial cells,human umbilical vein endothelial cells(HUVECs)were exposed to OA.Sirt6 gene silencing cells were generated through RNA interference.Cell viability was measured by SRB colorimetry,and cellular senescence was characterized by β-galactosidase(β-Gal)protein expression and in situ chromogenic reaction.Cell cycle distribution was detected by flow cytometry after PI staining.The protein and mRNA expression of cycle arrest factors,including p16,p21,and p53,were evaluated by Western blot and fluo-rescence quantitative PCR.The results showed that OA at 900 μmol/L significantly inhibited HUVECs prolifera-tion,while up-regulating[3-Gal protein expression and the proportion of positive staining cells after 72 hours of in-cubation.Moreover,OA incubation arrested the cells in the G0/G1 phase,as well as up-regulated the mRNA and protein expression of p21,p16,and p53.Nuciferine showed no obvious effect on the cell proliferation;however,it significantly antagonized the senescent phenotype and the overexpression of p21,p16,and p53 induced by OA.Molecular docking analysis showed that nuciferine had the strongest binding ability with Sirt6 in the Sirtuins family.OA markedly down-regulated Sirt6 mRNA and protein expression,which was significantly reversed by nuciferine.Silencing the expression of Sirt6 via small RNA interference abolished the modulating effect of nuciferine against the overexpression of senescent-related factors induced by OA.All these results suggested that nuciferine reversed OA-induced HUVECs senescence,which is mediated by the Sirt6 activation.关键词
血管内皮细胞衰老/脂毒性/荷叶碱/Sirt6Key words
vascular endothelial cell senescence/lipototoxicity/nuciferine/Sirt6分类
医药卫生引用本文复制引用
王玉娟,胡彦萍,何延浩,石晓冰,何杰,李刚,马成俊,王振华..荷叶碱逆转油酸诱导的血管内皮细胞衰老[J].烟台大学学报（自然科学与工程版）,2025,38(3):314-324,11.基金项目
山东省自然科学基金资助项目(ZR2019MH094). （ZR2019MH094）
