中国病理生理杂志2024，Vol.40Issue(6)：961-970,10.DOI:10.3969/j.issn.1000-4718.2024.06.001
硫化氢通过激活Akt抑制铁死亡减轻ox-HDL诱导的人脐静脉内皮细胞功能障碍
Hydrogen sulfide attenuates ox-HDL-induced endothelial impairment by Akt-mediated inhibition of ferroptosis in HUVECs
摘要
Abstract
AIM:To investigate the effect of hydrogen sulfide(H2S)on ferroptosis and functional impairment induced by oxidized high-density lipoprotein(ox-HDL)in human umbilical vein endothelial cells(HUVECs),and to ex-plore its mechanisms.METHODS:The HUVECs were cultured in vitro and exposed to 200 mg/L ox-HDL,ferroptosis in-hibitor ferrostatin-1(Fer-1),protein kinase B(PKB/Akt)inhibitor MK-2206 2HCl(MK),Akt agonist SC79,and/or H2S for 24 h.Western blot was used to identify the relevant proteins.Intracellular levels of reactive oxygen species(ROS)were analyzed by flow cytometry and immunofluorescence staining.Intracellular iron was measured using an iron detection kit.The number of monocytes adhering to endothelial cells was counted using the monocyte adhesion assay.RESULTS:Compared with control group,acyl-CoA synthetase long-chain family member 4(ACSL4)protein expression in ox-HDL group was elevated by 1.45-fold(P<0.01),glutathione peroxidase 4(GPX4)protein expression was decreased by 29.79%(P<0.05),and ROS levels and iron ion content were elevated by 4.81-fold and 1.40-fold,respectively(P<0.01).The ratios of p-PI3K/PI3K and p-Akt/Akt were decreased by 45.65%and 41.68%,respectively(P<0.01),endo-thelial cell function-related protein IL-6,ICAM-1 and TNF-α expression was elevated 1.18-fold,1.24-fold and 1.41-fold(P<0.05),respectively,eNOS protein expression was decreased by 35.24%(P<0.01),and monocyte adhesion was ele-vated 3.43-fold(P<0.01).Compared with ox-HDL group,the endothelial cell iron death-related protein ACSL4 was de-creased by 22.32%(P<0.05),GPX4 was increased by 1.27-fold(P<0.01),and the p-Akt/Akt ratio was increased by 1.52-fold(P<0.01)in ox-HDL+H2S group.The fluorescence microscopy results showed that the ROS was decreased by 50.35%(P<0.01).The IL-6,ICAM-1 and TNF-α protein expression was decreased by 13.34%,9.83%and 13.46%(P<0.05),respectively,eNOS was elevated by 1.22-fold(P<0.01),and the number of monocyte adhesion was de-creased by 59.05%(P<0.01).Compared with ox-HDL group,GPX4 protein expression in ox-HDL+SC79 group was ele-vated by 1.49-fold(P<0.01),ACSL4 expression was decreased by 20.72%(P<0.05),and ROS and iron ions were de-creased by 59.31%and 23.85%(P<0.05),respectively.Compared with ox-HDL+H2S group,GPX4 protein expression was decreased by 21.28%,and ACSL4 protein expression was increased by 1.16-fold in ox-HDL+H2S+MK group(P<0.05).CONCLUSION:H2S activates Akt to inhibit ox-HDL-induced ferroptosis in HUVECs and alleviate their func-tional damage.关键词
硫化氢/氧化高密度脂蛋白/人脐静脉内皮细胞/铁死亡/PI3K/Akt信号通路Key words
hydrogen sulfide/oxidized high-density lipoprotein/human vascular endothelial cells/ferropto-sis/PI3K/Akt signaling pathway分类
医药卫生引用本文复制引用
王燕霞,吴泽凡,易琪龙,刘宁雅,姜志胜..硫化氢通过激活Akt抑制铁死亡减轻ox-HDL诱导的人脐静脉内皮细胞功能障碍[J].中国病理生理杂志,2024,40(6):961-970,10.基金项目
国家自然科学基金资助项目(No.91839103 （）
No.81670429) （）
湖南省重点研发计划(湖南创新型省份建设专项经费资助 （）
No.2020SK2105) （）
