白藜芦醇对ox-LDL诱导的内皮细胞铁死亡影响

INFLUENCE OF RESVERATROL ON OX-LDL-INDUCED FERROPTOSIS IN HUMAN UMBILICAL VEIN ENDOTHELIAL CELLS

目的探讨白藜芦醇对氧化低密度脂蛋白(ox-LDL)诱导的人脐静脉内皮细胞(HUVECs)铁死亡的影响。方法利用ox-LDL诱导建立HUVECs铁死亡模型。实验设置对照组、ox-LDL组和白藜芦醇低、中、高剂量组。分别检测各组细胞存活率及细胞中丙二醛(MDA)、谷胱甘肽(GSH)、亚铁离子(Fe^(2+))、活性氧(ROS)水平;采用免疫印迹法及免疫荧光法检测细胞中谷胱甘肽过氧化物酶4(GPX4)、溶质载体家族7成员11(SLC7A11)和铁蛋白重链(FTH1)蛋白表达。结果与对照组相比,ox-LDL组细胞存活率及细胞中GSH、GPX4、SLC7A11和FTH1表达明显降低,MDA、Fe^(2+)和ROS水平显著升高;与ox-LDL组相比,白藜芦醇低、中、高剂量组细胞存活率及细胞中GSH、GPX4、SLC7A11和FTH1表达明显升高,MDA、Fe^(2+)和ROS水平显著降低,差异均有统计学意义(F=9.93~722.16,P<0.05)。结论白藜芦醇可能通过激活SLC7A11/GPX4信号通路保护HUVECs免受铁死亡的影响。

Objective To investigate the influence of resveratrol on oxidized low-density lipoprotein(ox-LDL)-induced ferroptosis in human umbilical vein endothelial cells(HUVECs).Methods The ferroptosis in HUVECs was induced by ox-LDL.In this study,control group,ox-LDL group,and low-,middle-,and high-dose resveratrol groups were set.Cell viability and levels of malondialdehyde(MDA),glutathione(GSH),ferrous ion(Fe^(2+)),and reactive oxygen species(ROS)in cells were measured.Western blot and immunofluorescence method were applied to measure the protein expression of glutathione peroxidase 4(GPX4),solute carrier family 7 member 11(SLC7A11),and ferritin heavy chain 1(FTH1)in cells.Results Compared with the control group,the ox-LDL group had significantly decreased cell viability and expression levels of GSH,GPX4,SLC7A11,and FTH1,and significantly increased MDA,Fe^(2+),and ROS levels.Compared with the ox-LDL group,the low-,middle-,and high-dose resveratrol groups had significantly increased cell viability and expression levels of GSH,GPX4,SLC7A11,and FTH1,and significantly decreased MDA,Fe^(2+),and ROS levels(F=9.93-722.16,P<0.05).Conclusion Resveratrol may protect HUVECs from ferroptosis by activating the SLC7A11/GPX4 signaling pathway.