国际生殖健康/计划生育杂志2026,Vol.45Issue(3):177-183,7.DOI:10.12280/gjszjk.20260180
脂质过氧化和铁死亡参与调节衰老卵巢颗粒细胞的实验研究
Experimental Study on the Involvement of Lipid Peroxidation and Ferroptosis in the Regulation of Senescent Ovarian Granulosa Cells
摘要
Abstract
Objective:To compare the levels of lipid peroxidation,iron accumulation and ferroptosis sensitivity between normal and senescent ovarian granulosa cells by the in vivo and in vitro experiments.Methods:The mitochondrial status and iron accumulation in the ovarian tissues of female C57BL/6 mice aged 3 months(reproductive active period)and 12 months(reproductive senescence)were detected in the in vivo experiment.In the in vitro experiment,the SVOG cell,the human ovarian granulosa cell line,was used to develope the senescence model by thapsigargin(TG).The cellular senescence-related markers,lipid peroxidation and ferroptosis-related markers were detected.Senescence-associated proteins such as P16,P21 and TP53 were included.Pro-inflammatory cytokines of the senescence-associated secretory phenotype(SASP),including interleukin-1A(IL-1 A),IL-1B,IL-6 and C-X-C chemokine ligand 8(CXCL8)were analyzed.The ferroptosis and lipid peroxidation indicators were also tested,including the expression levels of ferroptosis-related proteins[glutathione peroxidase 4(GPX4),transferrin receptor(TFRC),and nuclear receptor coactivator 4(NCOA4)],and the levels of reactive oxygen species(ROS),malondialdehyde(MDA),and ferrous ion(Fe2+).Results:The in vivo experiment confirmed a significant increase in the iron accumulation in senescence ovaries(P<0.01).The in vitro experiment confirmed that TG successfully induced the senescence model of SVOG cells and reduced cell viability(P<0.05).In the senescent cells,the expression of the ferroptosis-related protein GPX4 was decreased(P<0.000 1),while the expressions of TFRC and NCOA4 were increased(P<0.01).Furthermore,the levels of ROS,MDA and Fe2+,were all increased(P<0.01).Conclusions:Senescent ovarian granulosa cells display the iron accumulation and the elevated lipid peroxidation,and the increased ferroptosis sensitivity,indicating that ferroptosis participates in the regulation of ovarian granulosa cell aging.关键词
卵巢/细胞衰老/铁死亡/脂质过氧化作用/颗粒细胞Key words
Ovary/Cellular senescence/Ferroptosis/Lipid peroxidation/Granulosa cells引用本文复制引用
董思睿,孟艳..脂质过氧化和铁死亡参与调节衰老卵巢颗粒细胞的实验研究[J].国际生殖健康/计划生育杂志,2026,45(3):177-183,7.基金项目
国家自然科学基金(82271688) (82271688)