骨髓增生异常综合征（Myelodysplastic syndrome, MDS）是一类源于造血干/祖细胞损伤的异质性克隆性疾病，部分患者将会发展成急性白血病。该类疾病的显著病理特征是多系造血细胞数量减少，骨髓中存在大量的病态巨核细胞。氨磷汀是MDS和骨髓移植患者临床治疗的重要支持药物，能够改善患者的造血情况，但是其具体作用机制目前还不清楚。近期研究表明氨磷汀具有促进巨核细胞分化的功能。本论文在此研究基础上证明氨磷汀与细胞能量代谢相关，而且它通过诱导活性氧的产生来促进巨核细胞分化和成熟，从而促进血小板的产生，缓解MDS患者的症状。我们首先使用氨磷汀处理HEL细胞系，证明氨磷汀不仅可以抑制HEL细胞的增殖，也能促进巨核细胞标志蛋白CD41和CD42的表达，这表明氨磷汀是一种巨核细胞分化和成熟的诱导因子。而且，我们以不同浓度的氨磷汀处理HEL细胞，在不同时间点检测ROS水平，结果表明在6 h处理后，HEL细胞的ROS水平有显著提高，这说明氨磷汀可以诱导巨核细胞的ROS产生，进一步使用流式细胞术检测氨磷汀处理后HEL细胞的线粒体数量，发现氨磷汀可以促进HEL细胞的线粒体数量增多。据此，我们初步得到结论，氨磷汀可以通过诱导ROS水平上升来促进HEL细胞系分化，形成成熟的巨核细胞。进一步地，我们使用氨磷汀治疗经60Coγ射线照射的C57BL/6J小鼠，结果表明氨磷汀可以促进射线损伤小鼠骨髓造血干细胞的增殖，并且促进造血祖细胞的分化。实验初步证明了氨磷汀可以促进射线损伤小鼠的骨髓重建。

Myelodysplastic syndrome (MDS) is a clonal disease derived from hematopoietic stem/progenitor cell injury. It is characterized by hematopoietic failure, multiple hematopoietic cell reduction, and there are a large number of pathological megakaryocytes in the patient's bone marrow. Differentiation of megakaryocytes is an effective strategy to improve the symptoms of thrombocytopenia in patients. Amifostine is an important drug used clinically to therapy MDS and can improve the symptoms of thrombocytopenia in patients, but its mechanism remains unclear. We hypothesize that Amifostine may promote megakaryocyte's differentiation by inducing the production of reactive oxygen species, thereby increasing the number of platelets in patients. In the experiment, we firstly treat the HEL cell line with Amifostine, and finds that Amifostine can effectively inhibit the proliferation of HEL cells and enhance the expression of megakaryoblastic specific proteins CD41 and CD42, indicating Amifostine can promote the differentiation and maturation of megakaryocytes. Furthermore, we find that ROS level significantly increases in HEL cells with incubation with Amifostine, indicating that Amifostine can induce ROS production in megakaryocytes. Besides, The number of mitochondria in HEL cells treated with Amifostine increases significantly. Based on this, we initially conclude that Amifostine can promote the differentiation of HEL cell by inducing ROS production and the induction of ROS levels may be related to the increase amount of mitochondria. Further, we use Amifostine to treat C57BL/6J mice irradiated with 60Co γ-rays, and the results show that Amifostine can promote the proliferation of mouse bone marrow hematopoietic stem cells and promote the differentiation of hematopoietic progenitor cells. The experiment preliminarily proves that Amifostine can promote the reconstitution of bone marrow in radiation-injured mice.