铁蓄积骨质疏松小鼠模型造血干细胞与骨代谢指标的相关性

摘要

Objective To explore the correlation between hematopoietic stem cells (HSCs) and bone turnover markers in iron accumulation osteoporosis mice model .Preliminary discussing the role of iron accumulation osteoporosis in hematopoieticsystem.Methods 6-8weeksC57malemicewereintraperitoneallyinjectedwith0.1g/kgferricammoni-um citrate ( FAC ) for eight weeks, serum ferritin, osteogenesis marker procollagen type 1 N-terminal propeptide (P1NP), osteoclastic markers CTX, peripheralroutine blood were detected , using micro-CT for distal femur trabecular bone reconstruction of three dimensional form and spatial structure parameter analysis , HSCs accounts for the proportion of bone marrow cells were detected by flow cytometry , HSCs cell colony forming ability was measured . Results The ELISA results show that the FAC intervention group increased bone marrow HSCs proportion 4.01%±0.63% compared to control group 2.61%±0.43% ( P<0.05 ) , and HSCs cell colony formation 142/dish decreased compared to control group 47/dish; FAC group increased serum ferritin ( 13.27 ±0.72 ) μg/L compared to control group ( 4.14 ± 0.96) μg/L, decreased P1NP ( 4.62 ±0.76 ) ng/ml compared to control group ( 8.23 ±0.66 ) ng/ml, CTX (123.54 ±1.63) ng/ml increased compared to control group (83.36 ±1.89) ng/ml (P <0.05); FAC group in-creased peripheral blood platelet (1380 ±103) ×109/L compared to control group (1023 ±83) ×109/L (P<0.05);Micro-CT results showed FAC group lower BMD ( 50.41 ±10.27 ) mg/mm3 compared to control group ( 104.68 ± 8.56 ) mg/mm3 , bone trabecular space structure parameters decreased obviously [ BV/TV 10.18%±1.76%; Tb.Th (0.057 ±0.012) mm;Tb.N (1.02 ±0.21) N/mm] compared to control group [BV/TV 19.92%±1.92%; Tb.Th (0.098 ±0.008) mm; Tb.N (1.45 ±0.13) N/mm] (P<0.05).Conclusion Iron accumulation has significant effects on both bone turnover markers and HSCs .%目的：了解铁蓄积骨质疏松小鼠模型造血干细胞（hematopoietic stem cells， HSCs）指标变化及其与骨代谢指标变化的相关性，探讨骨质疏松范畴“铁蓄积”对造血系统的影响。方法6～8周C57雄性小鼠分为对照组、实验组，实验组用枸橼酸铁铵（ferric ammonium citrate， FAC）0.1 g／kg干预8周，两组均检测：血清铁蛋白（ferritin， FER）、胶原1型氨基端前肽（procollagen type 1 N-terminal propeptide， P1NP）、破骨标志物（ carboxy-terminal telopeptides ， CTX）、外周血血常规、股骨远端骨小梁三维形态重建和空间结构参数、 HSCs占骨髓细胞比例、 HSCs细胞集落形成能力，统计分析两组实验数据。结果实验组骨髓HSCs占骨髓比例4.01％±0.63％较对照组2.61％±0.43％显著升高（P＜0.05），实验组HSCs细胞集落形成142个／皿较对照组47个／皿显著增多；实验组血清铁蛋白（13.27±0.72）μg／L较对照组（4.14±0.96）μg／L显著升高，实验组P1NP （4.62±0.76） ng／ml较对照组（8.23±0.66） ng／ml显著降低，实验组CTX （123.54±1.63） ng／ml较对照组（83.36±1.89） ng／ml显著升高（P＜0.05）；实验组组外周血血小板（1380±103）×109／L较对照组（1023±83）×109／L显著升高（ P ＜0.05）；实验组 micro －CT 检测的骨密度（50.41±10.27） mg／mm3较对照组（104.68±8.56） mg／mm3显著下降、实验组骨小梁空间结构参数[bone volume／tissue volume， BV／TV；骨体积分数10.18％±1.76％； trabecula thickness， Tb.Th骨小梁厚度（0.057±0.012） mm； trabecula number， Tb.N骨小梁数（1.02±0.21） N／mm]较对照组[BV／TV （19.92％±1.92％）； Tb.Th （0.098±0.008） mm； Tb.N （1.45±0.13） N／mm]显著下降（P＜0.05）。结论在铁蓄积影响的骨质疏松模型中，铁蓄积不仅对骨代谢指标有显著影响，也对HSCs有显著影响。