中华骨质疏松和骨矿盐疾病杂志2024，Vol.17Issue(6)：587-596,10.DOI:10.3969/j.issn.1674-2591.2024.06.007
铁蓄积通过氧化应激-自噬对雌性SD大鼠骨代谢的影响及相关机制
Effect of iron excess on bone metabolism in female SD rats via oxidative stress autophagy and related mechanisms
摘要
Abstract
Objective To investigate the effects of iron excess on bone metabolism in female SD rats via oxida-tive stress autophagy and examine the underlying mechanisms.Methods A total of sixty female SD rats were randomly as-signed into sham operation(SHAM group),ovariectomy(OVX group),ovariectomy plus ferric ammonium citrate(OVX+FAC group),ovariectomy plus ferric ammonium citrate plus glutathione(OVX+FAC+GSH group)and ovariectomy plus ferric ammonium citrate plus deferoxamine(OVX+FAC+DFO group).ELISA was used to detect reactive oxygen species(ROS),N-terminal peptide of type Ⅰ collagen(PINP),bone specific alkaline phosphatase(B-ALP),C-terminal pep-tide of type Ⅰ collagen(CTX),and tartrate resistant acid phosphatase 5b(TRACP-5b)in rat serum.Micro CT scanning was performed,and bone microstructure was analyzed.Tibial autophagosomes were observed by transmission electron mi-croscopy.The expression of microtubule associated protein 1 light chain 3(LC3),forkhead box protein O3(FOXO3)and autophagy related gene 7(ATG7)proteins in the bone tissue were assessed by western blot.Results Serum ROS levels in the other groups significantly increased(P<0.01)compared to the SHAM group.Serum ROS levels in the OVX+FAC group were significantly higher(P<0.01)than in the OVX group.GSH and DFO considerably reduced serum ROS levels in ovariectomized rats with iron accumulation(P<0.05).The other groups'serum levels of P1NP,B-ALP,CTX and TRACP-5b were all higher(P<0.05)than the SHAM group,with the OVX+FAC group showing the most significant rise(P<0.01).GSH and DFO significantly lowered the serum levels of P1NP,B-ALP,CTX and TRACP-5b when compared to the OVX and OVX+FAC groups(P<0.01).Compared to the SHAM group,the trabecular bone mineral density(Tb.BMD),percent bone volume(BV/TV),trabecular number(Tb.N)and trabeculae thickness(Tb.Th)in the other groups of rats were significantly reduced(P<0.05),while trabecular separation(Tb.SP),trabecular pattern factor(Tb.Pf)and structure model index(SMI)increased significantly(P<0.05),with the OVX+FAC group exhibiting the most significant changes(P<0.05).GSH and DFO increased Tb.BMD,BV/TV,Tb.N and Tb.Th in rats(P<0.05),while reducing Tb.Sp,Tb.Pf and SMI(P<0.05)compared to the OVX and OVX+FAC groups.DFO improves Tb.BMD,BV/TV and TB.N and Tb.Pf significantly(P<0.05)compared to GSH.There was an increase(P<0.05)in the LC3-Ⅱ/LC3-Ⅰ ratio,the expression of FOXO3 and ATG7 protein in the bone tissue of other groups of rats,and a rise in the number of autophagosomes,with the largest increase(P<0.01)in the OVX+FAC group compared to the SHAM group.GSH and DFO reduced the LC3-Ⅱ/LC3-Ⅰ ratio and downregulate the expression of FOXO3 and ATG7 pro-teins in bone tissue(P<0.05)compared to the OVX and OVX+FAC groups.They could also reduce the amount of auto-phagosomes.Conclusion Iron excess can activate FOXO3 via ROS production to promote autophagy,leading to decreased bone mass and osteoporosis.Antioxidants and iron reduction can help to increase bone mass.关键词
铁蓄积/活性氧/自噬/骨代谢Key words
iron excess/reactive oxygen species/autophagy/bone metabolism分类
医药卫生引用本文复制引用
赵理平,陈国兆,张益,王黎明,沙卫平..铁蓄积通过氧化应激-自噬对雌性SD大鼠骨代谢的影响及相关机制[J].中华骨质疏松和骨矿盐疾病杂志,2024,17(6):587-596,10.基金项目
苏州市民生科技-医疗卫生应用基础研究项目(SYSD2020007) （SYSD2020007）
