赣南医科大学学报2025，Vol.45Issue(3)：211-217,7.DOI:10.3969/j.issn.1001-5779.2025.03.001
铁蓄积对老年雌性小鼠骨代谢影响的实验研究
Experimental research of the impact of iron accumulation on bone metabolism in elderly female mice
摘要
Abstract
Objective:To investigate the effects of chronic iron accumulation on bone microstructure,osteogenesis,and osteoclastogenesis in aged female mice,an endogenous iron accumulation model was developed by knocking out the Hepcidin 1(Hepc1)gene.The study also aimed to clarify the underlying mechanisms of these effects.Methods:Hepc1 heterozygous mice were bred,and offspring were divided into two groups based on genotyping:wild-type(WT)group and Hepc1 knockout(KO)group,with six mice in each group.At the age of 18 months,the mice were sacrificed,and atomic absorption spectrometry along with Perl's staining were employed to evaluate and compare the iron accumulation status between the two groups of mice.ELISA was used to detect the levels of estradiol,iron metabolism markers and bone turnover markers in the serum of mice.The bone microstructure was observed by Micro-CT.q-PCR was used to determine the expression of genes related to bone formation and bone resorption.The level of oxidative stress was detected by chemical colorimetry.Results:There was no significant difference in body weight and estradiol levels between the two groups(P＞0.05).Compared with the WT group,the hepcidin content in the KO group was significantly decreased(P＜0.001),while the contents of serum ferritin,liver and tibial iron were significantly increased(P＜0.001),and Perl's staining also confirmed that there was iron deposition in the liver tissue of the KO group.Compared with the WT group,done mineral density,trabecular thickness,bone volume fraction,trabecular number and connectivity density in the KO group were significantly decreased(P＜0.05),and trabecular separation and structure model index were significantly increased(P＜0.05);the cortical bone area also decreased(P＜0.05).The expressions of osteoclast-related genes such as CTSK,MMP9,OPG,TRAP and RANKL and the level of C-terminal telopeptide of type Ⅰ collagen(CTX)in the KO group were higher than those in the WT group(P＜0.05),while the expressions of osteogenesis-related genes such as ALP,COL-1,OCN,RUNX2 and SP7 and the level of osteocalcin(OCN)were lower than those in the WT group(P＜0.05).The level of superoxide dismutase(SOD)in the KO group was significantly lower than those in the WT group,while the level of malondialdehyde(MDA)was higher than those in the WT group(P＜0.001).Conclusion:Mice with Hepc1 gene knockout exhibits chronic iron accumulation,which exacerbates bone loss by inhibiting osteogenesis and promoting osteoclastogenesis.The mechanism may be related to the increased level of reactive oxygen species.关键词
铁调素/铁蓄积/骨转换/氧化应激Key words
Hepcidin/Iron accumulation/Bone turnover/Oxidative stress分类
历史学引用本文复制引用
朱胤,刘禄林,刘中瑞,刘桂文,韩皓衍,肖春林,肖建华,叶勇军,黄为民,刘午阳..铁蓄积对老年雌性小鼠骨代谢影响的实验研究[J].赣南医科大学学报,2025,45(3):211-217,7.基金项目
国家自然科学基金地区项目(82260649) （82260649）
江西省自然科学基金资助项目(20232BAB216028) （20232BAB216028）
