铁蓄积及去铁胺干预对雄性小鼠骨量变化的影响  

Effects of deferoxamine and iron overload on bone mass of male mice

作　　者：袁晔[1] 易剑桥[1] 徐非[2] 王亮[1] 杨帆[3] 张辉[1] 徐又佳[1] 

机构地区：[1]苏州大学附属第二医院骨科,苏州215004 [2]苏州大学唐仲英医学研究院血液学研究中心,苏州215123 [3]苏州大学骨质疏松症诊疗技术研究所,苏州215004

出　　处：《中华骨质疏松和骨矿盐疾病杂志》2017年第2期125-129,共5页Chinese Journal Of Osteoporosis And Bone Mineral Research

基　　金：国家自然基金(81273090);(81500680);江苏省临床专项(BL2014044);苏州市卫生局项目(LCZX201305);优势学科群(XKQ2015001)

摘　　要：目的了解铁蓄积雄性小鼠骨量变化及降铁剂去铁胺(deferoxamine,DFO)干预后骨量改变。方法在体实验,选取18只6~8周C57雄性小鼠分为对照组(Ctrl组)、铁蓄积组(FAC组)、DFO干预组(FAC+DFO组),铁蓄积组使用枸橼酸铁铵(ferric ammonium citrate,FAC)干预8周(每周0.1 g/kg),DFO干预组在制作铁蓄积组的第4周FAC注射后1h腹腔注射DFO每周0.2 g/kg。8周后各组均检测:血清铁蛋白(ferritin,FER)、股骨远端骨小梁三维形态重建和空间结构参数。体外实验:使用MC3T3细胞,分为对照组(Ctrl组)、铁蓄积组(FAC组)、DFO干预组(FAC+DFO组);FAC组加FAC干预48 h,DFO组在FAC干预24 h时加入DFO;48 h后收集3组细胞,检测指标:细胞碱性磷酸酶(alkaline phosphatase,ALP)活性、骨形成蛋白(bone morphogenetic protein 2,BMP2)表达。结果 micro-CT检测提示Ctrl组BMD(104.68±8.56)mg/m^3,BV/TV(19.92±1.92)%,Tb.Th(0.098±0.008)mm,Tb.Sp(0.172±0.133)mm,ALP活性值0.71±0.06;FAC组BMD(50.41±10.27)mg/m^3,BV/TV(10.18±1.76)%,Tb.Th(0.057±0.012)mm,Tb.Sp(0.322±0.214)mm,ALP活性值0.33±0.04;FAC+DFO组BMD(92.72±9.62)mg/m^3,BV/TV(17.84±1.54)%,Tb.Th(0.085±0.010)mm,Tb.Sp(0.186±0.195)mm,ALP活性值0.59±0.03。FAC组相比于Ctrl组骨密度、骨小梁空间结构参数显著下降,成骨细胞ALP活性受抑制,BMP2表达与Ctrl组比较降低,差异有统计学意义(P<0.05);DFO干预后骨密度恢复,骨小梁空间结构参数恢复正常,ALP和BMP2表达恢复正常,与FAC组比较,差异有统计学意义(P<0.05)。结论雄性小鼠铁蓄积后骨量显著下降,DFO干预可以缓解铁蓄积相关的骨量减低,其机制可能与DFO阻断铁蓄积对BMP2的抑制有关。Objective To study the effects of deferoxamine （DFO） and iron overload on bone mass of male mice. Methods 6 to 8 weeks old C57 mice were divided into control group （ Ctrl group） , iron accumulation group （ FAC group） , DFO intervention group （ FAC ＋ DFO group）. FAC group were intervened for 8 weeks using ferric am- monium citrate （FAC） 0. 1 g/kg. DFO intervention group was injected 1 hour after FAC intervention from 4 to 8 weeks. Each group were tested： serum ferritin （FER） , distal femur trabecular bone reconstruction of three dimensional form and spatial structure parameters. In vitro experiments MC3T3 cells were divided into Ctrl group, FAC group, FAC ＋ DFO group. FAC group were intervened for 48 hours by FAC, FAC ＋ DFO group were intervened by FAC for 24 hours and joined DFO for 24 -48 hours. The cells of three groups were collected after 48 hours and alkaline phosphatase （ALP） activity, bone morphogenetic protein 2 （BMP2） expression were tested. Results Compared with control group [ bone mineral density （BMD） （ 104. 68 ± 8.56） mg/mm3, BV/TV （ 19.92 ± 1.92） %, Tb. Th （0. 098 ± 0. 008） mm, Tb. Sp （0. 172 ± 0. 133 ） ram, ALP activity value of 0. 71 ±0. 061 , structural parameters of trabecular bone space [FAC group： BMD （50.41 ± 10.27） mg/mm3, BV/TV （10. 18 ± 1.76）%, Tb. Th （0.057 ±0.012） mm, Tb. Sp （0. 322 ± 0. 214） ram, ALP activity value of 0. 33 ± 0. 04 ; FAC ＋ DFO group： BMD （92.72 ± 9.62） mg/mm3 , BV/ TV （ 17.84 ± 1.54） %, Tb. Th （0. 085 ± 0. 010） nun, Tb. Sp （0. 186 ± 0. 195 ） mm, ALP activity value of 0. 59 ± 0. 03 1 decreased in FAC group, osteoblast ALP activity and BMP2 were inhibited compared with Ctrl group （ P 〈 0. 05 ） ; DFO alleciated the trend. Conclusion DFO had therapeutic effect on iron overload induced inhibition of osteogenesis, and the mechanism may be related to DFO blocked inhibition of iron accumulation on BMP2.

关 键 词：铁蓄积 小鼠 雄性 骨质疏松 去铁胺 

分 类 号：R681[医药卫生—骨科学]