HIF-1α在照射损伤铁过载疾病红系造血中的表达及意义

发布时间：2018-06-27 22:36

本文选题：HIF-α + 雷帕霉素　；参考：《中国实验血液学杂志》2017年03期

【摘要】：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(P0.05)。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(P0.05)。IR和IO组HIF-1α相关信号分子表达明显高于Ctrl组(P0.05)。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(P0.05)。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。
[Abstract]:Aim: to study the expression of hypoxia inducible factor (hypoxia inducible factor-1 伪 (HIF-1 伪) in irradiated mice and its effect on hematopoiesis. Methods Twenty mice were randomly divided into 4 groups: Ctrl (control) IR (iron-overload) and rapamycin (Rapamycin) to verify the iron overload model. FCM was used to detect the expression of HIF-1 伪 and related signal molecules in bone marrow cells by flow cytometry (FCM). The ratio of early Ter119 ~ CD71- and late Ter119- CD71- was detected by reverse transcription-polymerase chain reaction (RT-PCR). Results the expression of HIF-1 伪 in the two groups was significantly higher than that in the Ctrl group, and the ratio of BFU-E and CFU-E in the IO group was significantly higher than that in the IR group (P0.05) and the ratio of CFU-E to CFU-E in the IO group was significantly lower than that in the Ctrl group. The expression of HIF-1 伪 related signal molecules in IO group was significantly lower than that in IR group (P0.05) and the expression of HIF-1 伪 related signal molecule in IO group was significantly higher than that in Ctrl group (P0.05). The expression of HIF-1 伪 and related signal molecules decreased significantly (P0.05) after the application of mTOR inhibitor RAPA. Conclusion: irradiation can increase the expression of HIF-1 伪, decrease the proportion of erythropoiesis colony and primitive erythrocyte in late stage, and iron overload can aggravate the damage. Rapamycin alleviates partial injury, suggesting that iron overload may damage erythropoiesis by HIF-1 伪.
【作者单位】：天津医科大学第一中心临床学院天津市第一中心医院血液科;
【基金】：国家自然科学基金资助项目(81041043) 天津市自然科学基金重点项目(17JCZDJC35800) 天津市卫计委科技基金(2015KR15)
【分类号】：R457.1

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