去铁斯若治疗去卵巢小鼠铁蓄积骨量下降

摘要

目的 观察去铁斯若(deferasirox,DFR)对加枸橼酸铁铵(ferric ammonium citrate,FAC)铁蓄积绝经后小鼠骨丢失的治疗作用.方法 32只2月龄小鼠采用数字表法随机分为4组.假手术(Sham)组采用0.9%氯化钠注射液干预;去卵巢(ovariectomy,OVX)对照组切除双侧卵巢;去卵巢(OVX+FAC)组切除双侧卵巢后给予枸橼酸铁铵80 mg/kg(溶于0.9%氯化钠注射液)腹腔注射,每周3次,共持续5周;去卵巢加枸橼酸铁铵加去铁斯若(OVX+FAC+DFR)组在枸橼酸铁铵干预基础上给予去铁斯若100 mg/kg(溶于0.9%氯化钠注射液)灌胃,每周5次,持续6周.最后检测各组铁蛋白水平、骨铁含量以及股骨远端松质骨micro-CT扫面分析和三维重建.结果 血清铁蛋白、骨Perl`s染色提示OVX+FAC组铁蛋白(220.7±28.3)μg/L,显著高于Sham组(112.8±6.0)μg/L和OVX组(103.8±22.4)μg/L,DFR干预后OVX+FAC+DFR组铁蛋白(151.5±36.1)μg/L有所下降,差异有统计学意义(P<0.05).三维重建示OVX+FAC组小鼠骨小梁稀疏,骨密度(0.074±0.010)mg/mm3减低,DFR干预后骨小梁稍有增加,骨密度(0.110±0.015)mg/mm3显著恢复.结论 DFR可部分逆转铁蓄积导致的骨量下降,从而提高骨密度,改善骨微结构.%Objective To explore the effect of deferasirox(DFR) on bone mass and construction in ovariectomy(OVX) mice with iron accumulation by feeric ammonium citrate (FAC).Methods Thirty-two month old C57 mice were randomly divided into 4 groups.Sham group received saline treatment.Mice in OVX group were experienced ovariectomy.Mice in OVX+FAC group received intraperitoneal FAC 80 mg/kg for 5 weeks after ovariectomy.As for mice in OVX+FAC+DFR group,after ovariectomy and FAC treatment,the iron accumulated mice received DFR treatment for 6 weeks.At last,we detected serum ferritin levels,bone iron levels and bone three-dimensional reconstruction.Results Serum ferritin levels and Perl`s blue staining of bone suggested that iron levels in mice of OVX+FAC group(ferritin 220.7±28.3μg/L) were significantly higher than those in Sham group(112.8±6.0 μg/L) and OVX group(103.8±22.4 μg/L).After the treatment of DFR,the iron levels were decreased.3D reconstruction suggested decreased cancellous bone parameters and bone mineral density(0.074±0.010 mg/mm3).After DFR treatment,the bone mineral density(0.110±0.016 mg/mm3) and trabecular bone were increased.ConclusionDFR could improve bone mineral density and improve bone micro-construction by reducing iron accumulation.