中国比较医学杂志2026，Vol.36Issue(3)：36-45,10.DOI:10.3969/j.issn.1671-7856.2026.03.003
同型半胱氨酸调控FOXO3a介导线粒体损伤在代谢相关脂肪性肝病中的作用
Homocysteine regulates FOXO3a to mediate mitochondrial damage in metabolism-associated fatty liver disease
摘要
Abstract
Objective To investigate the effects and mechanism of homocysteine(Hcy)-regulated FOXO3a-mediated mitochondrial damage in metabolic dysfunction-associated fatty liver disease(MAFLD).Methods Six-week-old Cbs+/-mice(n=12)were divided randomly into two groups and fed a normal diet group(ND group)or a high-methionine diet group(HMD group),respectively,for 12 weeks(n=6 mice per group).The inhibition rate of hepatocytes after treatment with different concentrations(0、50、100、150 μmol/L)of Hcy was detected by the Cell Counting Kit-8 Kit.NCTC1469 normal mouse hepatocytes were divided into the following groups:Control group,Hcy intervention group(Hcy group,100 μmol/L Hcy),negative control(NC)small interfering(si)RNA-transfected group(si-NC group),FOXO3a siRNA-transfected group(si-FOXO3a group),NC siRNA-transfected with Hcy intervention group(Hcy+si-NC group),and FOXO3a siRNA-transfected with Hcy intervention group(Hcy+si-FOXO3a group).Liver tissue injury was observed by HE staining and the distribution and accumulation of lipid droplets in hepatocytes was detected by Oil Red O staining.Total cholesterol(TC)and triglycerides(TG)were analyzed to indicate the lipid metabolite contents of the cells.FOXO3a protein expression in liver tissues(ND group and HMD group)and liver cells(Control group and Hcy group)were detected by Western blot.Reactive oxygen species(ROS)were measured to indicate the degree of oxidative stress in cells.Mitochondrial membrane potential was detected using JC-1 and morphological changes in mitochondria were observed using Mito-tracker.Changes in mtDNA expression were detected by quantitative reverse transcription-polymerase chain reaction.Results Liver tissue structure was disordered in the HMD group compared with the ND group,hepatocytes were enlarged,the cytoplasm was loose and lightly stained,and a large number of vacuoles and lipid droplets were observed in the liver cells.The number of Oil Red O-positive lipid droplets was increased in the Hcy group compared with the Control group,and TC and TG levels were increased(P<0.001).Expression levels of FOXO3a protein were significantly increased in the HMD group and Hcy group compared with the ND group and Control group(P<0.05).Intracellular ROS levels were decreased in the Hcy+si-FOXO3a group compared with the Hcy+si-NC group,and JC-1 monomer,mitochondrial fragmentation,mtDNA expression level,the number of Oil Red O-positive lipid droplets,and TC level and TG level were also all decreased(P<0.01,P<0.001).Conclusions FOXO3a plays an important promoting role in lipid metabolic disorders of MAFLD caused by Hcy by regulating mitochondrial damage.关键词
FOXO3a/线粒体/Hcy/MAFLDKey words
FOXO3a/mitochondria/Hcy/MAFLD分类
医药卫生引用本文复制引用
焦运,姜怡邓,张婕,刘惠娟,杨佳琪,王雅菁,刘虹麟,马芳,李桂忠,张慧萍..同型半胱氨酸调控FOXO3a介导线粒体损伤在代谢相关脂肪性肝病中的作用[J].中国比较医学杂志,2026,36(3):36-45,10.基金项目
国家自然科学基金项目(82460120) （82460120）
宁夏自然科学基金项目(2024AAC03592) （2024AAC03592）
宁夏医科大学校级重点项目(XJKF240311) （XJKF240311）
癌症、心脑血管、呼吸和代谢性疾病防治研究国家科技重大专项(2024ZD0531200) （2024ZD0531200）
宁夏回族自治区重点研发计划重点项目(2023BEG02074) （2023BEG02074）
湖南省卫生健康高层次人才重大科研专项(R2023120). （R2023120）
