关键词: 铁过载, 动物模型, 辐射损伤, 间充质干细胞, 活性氧

Abstract: Objective To establish a mouse normal and irradiational injured(IR) bone marrow mesenchymal stem cells(MSCs) iron overload model, explore the effects of iron overload on murine bone marrow MSCs and the possible mechanism in this process. Methods Forty male mice(C57BL/6) were randomly divided into four groups:control,iron overload ,IR and IR with iron treated groups (n-10 group),Iron dextran was injected intraperitoneally (i.p.) at 25mg/ml every 3 day to establish the iron overload model, while control and IR group received saline for 4 weeks. Isolation and culture of mesenchymal stem cells from mouse compact bone. The levels of labile iron pool ( LIP) and reactive oxygen species (ROS) were measured to confirm oxidative stress state in the model.Cell prolifiration was measured through population double time (DT) and cck8 assay.The osteoblastic differentiation ability was assessed by Alkaline phosphatase (ALP) activity ,alizarin red stain and the osteogenic gene expression. Result Compared with control and IR groups,iron deposite increased significently in Fe and IR+Fe groups, The LIP level of MSCs was also increased by iron dextran treatment（P<0.05）. The level of intracellular ROS with two iron overload groups was higher than that of the control and IR groups.The prolifiration ability of Fe and IR+Fe groups was lower than control and IR group(p<0.05).The osteoblastic differentation ability of experimental group was supressed by iron overload induced by ROS. Conclusion Iron overload may impair the proliferation and differentation ability of normal and IR injured bone marrow MSCs by enhancing the generation of ROS.

Key words: iron overload, animal model, irradiational injury, mesenchymal stem cell, ROS