OBJECTIVETo study the expression of hypoxia inducible factor 1α(HIF-1α) of iron-overloaded in irradiated mice and its effect on erythropoiesis.

METHODSTwenty mice were randomly divided into 4 groups: Ctrl (control group), IR (irradiation group), IO (irradiation + iron overload group), and RAPA (rapamycin treatment group). The iron overload model was verified. The CFU-E (colony forming unit-erythroid) and BFU-E(burst colony forming unit-erythroid) were cultured; flow cytometry was used to detect the ratios of early stage (Ter119CD71) to late stage (Ter119CD71) of primitive erythroblasts; RT-PCR was used to detect the mRNA expression of HIF-1α and its related signal molecules in bone marrow cells.

RESULTSThe expression of HIF-1α in IR and IO group was significantly higher than that in Ctrl group, and that in IO group was significantly higher than IR group (P<0.05). The ratio of late stage primitive erythroblasts, the number of CFU-E and BFU-E in both IR and IO group were lower than those in Ctrl group, and those in IO group were significantly lower than those in IR group (P<0.05). Compared with Ctrl group, the expression of HIF-1α related signal pathway molecules in both IR and IO group was significantly decreased (P<0.05). Compared with IO group, the expression of HIF-1α and its related signal molecules in RAPA(mTOR inhibitor) group was decreased significantly (P<0.05), the number of BFU-E was increased significantly(P<0.05).

CONCLUSIONIrradiation induces the increase of HIF-1α and the decrease of the ability of hematopoietic colony formation and the ratio of late stage primitive erythroblasts. Iron overload can aggravate the injury. mTOR inhibitor rapamycin can partially alleviate the injury, suggesting that iron overload can lead to injury of erythropoiesis through HIF-1α.