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OA北大核心CSTPCD

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.