中国骨质疏松杂志

铁调素敲除对雄性小鼠铁代谢及骨代谢影响的实验研究

Experimental study on the effect of Hepcidin1 knockout on iron metabolism and bone metabolic in male mice

DOI：10.3969/j.issn.1006-7108.2023.02.001

英文关键词:iron accumulation hepcidin bone turnover oxidative stress

基金项目:江西省教育厅青年项目（GJJ201540）；江苏省临床重点项目（BE2019661）

作者	单位
刘禄林1 江小伟2 廖直斌2 赖长君2 张福生2 曹子厚3 刘午阳1 姬广林1 徐又佳3*	1. 赣南医学院第一附属医院骨科，江西赣州341000 2. 宁都县人民医院骨科，江西赣州3428003 3. 苏州大学附属第二医院骨科，江苏苏州215000

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中文摘要:

目的利用铁调素基因敲除雄性小鼠构建铁蓄积小鼠模型，观察小鼠铁代谢指标以及骨微结构的改变，探讨慢性铁蓄积对小鼠骨转换、氧化应激指标的动态作用。方法根据基因鉴定将小鼠分为铁调素敲除组（KO组）与野生型组（WT组），正常饮食，分别在7、12、18月龄作为观察点，检测小鼠体重、胫骨铁含量，肝脏铁染色，分析小鼠股骨骨微结构，检测血清铁调素、铁蛋白、骨转换指标骨钙素（OCN）、I型胶原羧基末端肽（CTX）水平以及反映氧化应激水平的血清丙二醛（MDA）、超氧化物歧化酶（SOD）水平。结果比较两组小鼠体重无明显差异，各时间点KO组小鼠的血清铁调素指标均显著低于WT组小鼠，KO组小鼠的血清铁蛋白、肝铁、骨铁含量均显著高于WT组小鼠；KO组小鼠纵向比较提示随着年龄增大，铁蓄积越来越明显。Micro-CT 结果显示，与WT组小鼠比较，KO组松质骨BMD、Tb.Th、BV/TV、Tb.N、ConnD均显著下降（P<0.05），Tb.Sp、SMI显著升高（P<0.05）。KO组小鼠皮质骨面积低于WT组小鼠。横向同年龄比较，KO组小鼠的血清OCN、SOD水平均显著低于WT组小鼠（P<0.05），而CTX除7月龄时无明显差异，在12、18月龄时均显著高于WT组小鼠，MDA水平各时间点KO组均高于WT组小鼠（P<0.05）。结论铁调素基因敲除后小鼠出现慢性累积性铁蓄积，铁蓄积可刺激氧化应激水平提高，并通过抑制成骨活性、促进破骨吸收而加重骨量丢失。

英文摘要:

Objective Iron accumulation model was constructed by hepcidin1 gene knockout in male mice, the changes of iron metabolism indexes and bone microstructure were observed, and the dynamic effects of chronic iron accumulation on bone turnover and oxidative stress indexes were explored. Methods According to the genotype mice were divided into 2 groups, hepcidin1 knockout mice group (KO) and wild type mice group(WT). The mice were fed with normal diet. Serum, liver, femur and tibia of mice were collected at 7, 12 and 18 months of age. The body weight of mice was measured and the iron content tibia was analyzed by atomic absorption spectrometry (ICP). Iron were stained on liver sections by Prussian blue staining. Micro-computed tomography (Micro-CT) was used to detect the microstructure of mouse femur bone. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum levels of hepcidn, ferritin, osteocalcin (OCN), type I collagen carboxy-terminal peptide (CTX). Serum malondialdehyde (MDA) and superoxide dismutase (SOD) levels reflecting oxidative stress levels were detected . Results There was no significant difference in body weight between the two groups. In KO group the serum Hepcidin level was significantly lower than that in WT group at each time point, while serum ferritin , iron content in liver and tibia were significantly higher in KO group. The longitudinal comparison showed that KO group presented gradually increasing iron accumulation. Micro-CT results showed that compared with WT group, BMD, Tb.Th, BV/TV, Tb.N and ConnD of cancellous bone in KO group were significantly decreased (P<0.05), while TB.Sp and SMI were significantly increased (P<0.05). Cortical bone area in KO group was lower than that in WT group. Transverse comparison showed that serum OCN and SOD levels in KO group were significantly lower than WT group（P<0.05）, while CTX levels in KO group were significantly higher than WT group at 12 months and 18 months except for 7 months, and MDA levels in KO group were higher than WT group at all time points（P<0.05）. Conclusion After hepcidin1 gene knockout, mice developed chronic cumulative iron accumulation, which can stimulate oxidative stress and aggravate bone loss by inhibiting osteogenic activity and promoting osteoclast absorption.

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