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目的:研究铁过载状态下缺氧诱导因子(hypoxia inducible factor-1α,HIF-1α)在照射损伤小鼠体内的表达及其对红系造血的影响和机制。方法:20只小鼠随机分成Ctrl(对照)、IR(单纯照射损伤)、IO(照射损伤+铁过载)和RAPA(雷帕霉素给药)共4组,验证铁过载模型;培养红系集落:CFU-E(红系集落形成单位)和BFU-E(爆式红系集落形成单位);流式细胞术检测骨髓原始红细胞:早期Ter119~+CD71~+和晚期Ter119~+CD71~-的比例;RT-PCR检测骨髓细胞HIF-1α及相关信号分子表达。结果:IR和IO组的HIF-1α的表达均较Ctrl组明显升高,且IO组明显高于IR组(P<0.05)。IR和IO组的晚期红细胞比例、BFU-E和CFU-E数目均较Ctrl组明显降低,且在IO组明显低于IR组(P<0.05)。IR和IO组HIF-1α相关信号分子表达明显高于Ctrl组(P<0.05)。应用mTOR抑制剂RAPA时HIF-1α及相关信号分子的表达明显降低,BFU-E明显升高(P<0.05)。结论:照射使HIF-1α表达升高,红系造血集落和晚期原始红细胞比例下降,铁过载更加重了损伤。雷帕霉素可缓解部分损伤,提示铁过载可通过HIF-1α介导损伤红系造血。
AIM: To investigate the expression of hypoxia inducible factor-1α (HIF-1α) in irradiated mice and its mechanism and effect on erythroid hematopoiesis. Methods: Twenty mice were randomly divided into 4 groups: control (Ctrl), IR (irradiation alone), IO (radiation injury + iron overload) and RAPA (rapamycin administration) CFU-E (erythroid colony forming units) and BFU-E (blastic red colony forming units) were detected by flow cytometry. The bone marrow erythrocytes were detected by flow cytometry in early stage of Ter119 ~ + CD71 ~ + and late Ter119 ~ + CD71 ~ The ratio of HIF-1α and related signal molecules in bone marrow cells was detected by RT-PCR. Results: The expression of HIF-1α in IR group and IO group was significantly higher than that in Ctrl group, and significantly higher in IO group than in IR group (P <0.05). The numbers of late erythrocytes, BFU-E and CFU-E in IR and IO groups were significantly lower than those in Ctrl group and significantly lower in IR group than in IR group (P <0.05). The expression of HIF-1α related signal molecules in IR and IO group was significantly higher than that in Ctrl group (P <0.05). The expression of HIF-1α and related signal molecules was significantly decreased and the BFU-E was significantly increased (P <0.05) when mTOR inhibitor RAPA was used. Conclusion: The expression of HIF-1α is increased by irradiation, the proportion of erythrocytic hematopoietic colony and late primitive erythrocyte is decreased, and the overload of iron is more serious. Rapamycin can alleviate some of the damage, suggesting that iron overload mediated erythroid hematopoiesis through HIF-1α.