中文摘要：

辐射可以通过引起造血干细胞（hematopoietic stem cell，HSC）内活性氧（reactive oxygen species，ROS）系统水平升高导致HSC损伤。HSC损伤患者出现难治性血液系统疾病，严重影响患者生存质量，甚至威胁患者生命。ROS可以通过多种机制引起组织、器官和细胞损伤。ROS的来源包括：线粒体、NOX（NADPH oxidases）、细胞色素P450酶、黄嘌呤氧化酶、非偶联NO合酶。已证实HSC内ROS来源于NOX。ROS升高后影响HSC在成骨细胞微环境定位，导致HSC与微环境相互作用减弱，从而影响HSC功能。此外，ROS升高后通过激活P38MAPK-P16Ink4途径，损伤HSC自我更新能力，并且使HSC定向分化产生更多的髓系克隆而不是红细胞系克隆；P13K—Akt-mTOR途径可能也是ROS诱导HSC损伤途径。ROS对细胞周期影响为：促使HSC离开G0期进入细胞周期，导致干细胞池的耗尽。基于NOX在氧化还原信号传递过程中的重要作用，证实辐射通过NOX产生的ROS以及鉴定产生ROS的NOX亚型，这一工作会为临床靶向治疗辐射诱发的血液系统疾病提供重要的价值。

英文摘要：

Ionizing radiation（IR） exposure may increase ROS level in HSC and lead to irreversible damage on HSC. ROS damages cells, tissues and organs through several pathways. Mitochondria, NADPH oxidases（NOX）, cytochrome P450-based enzymes, xanthine oxidase and uncoupled NO synthases can induce cellular ROS production. It has been suggested that ROS produced partly by NOX in HSC and could affect HSC＇s localization in their niche and reduce the interaction between the HSC and microenvironment. P38MAPK-P16Ink4 signaling pathway is activated by elevation of ROS, which might destroy the long-term maintenance of self-renewal and induce myeloid differentiation skewing. ROS have also been known to activate PI3K-Akt-mTOR signaling pathway. It can also inhibit maintenance of HSC quiescent state. It is significant to elucidate the mechanisms that ROS generated by NOX after HSC exposed to IR.