Hypoxia inducible factor 1alpha signaling in fractionated radiation-induced lung injury: role of oxidative stress and tissue hypoxia.
Hypoxia inducible factor 1alpha signaling in fractionated radiation-induced lung injury: role of oxidative stress and tissue hypoxia.
复制标题
DOI：
10.1667/rr1816.1
复制
发表时间：
2010-02
影响因子：
3.4
通讯作者：
Vujaskovic Z
中科院分区：
文献类型：
--
作者：
Rabbani ZN;Mi J;Zhang Y;Delong M;Jackson IL;Fleckenstein K;Salahuddin FK;Zhang X;Clary B;Anscher MS;Vujaskovic Z
为探讨缺氧诱导因子1α信号与氧化应激、组织缺氧、血管生成和炎症的关系，雌性Fischer 344大鼠右侧胸腔接受分次照射，剂量为40Gy8Gy5天。分别于照射前、照射后4、6、10、14、18、22、26周取肺组织，用免疫组织化学和Western印迹方法检测缺氧(HIF1OHdG)、氧化应激(8OHdG)、血管生成/毛细血管增殖(α/CD105)、巨噬细胞活化(ED-1)和细胞信号转导/纤维化(NF-κB、β-1)等生物学指标。HIF1α染色早在照射后4周即可观察到，并随照射时间的延长而明显增强。重要的是，HIF1α水平与氧化应激(8-OHdG)、组织缺氧(匹莫硝唑和CAIX)以及巨噬细胞聚集与炎症反应相一致。免疫组织化学检测结果表明，照射后肺组织中HIF1α表达的变化与肺组织中转化生长因子β1、血管内皮生长因子、核因子κB和CD105水平的变化相一致。这些结果支持氧化应激和组织缺氧可能是照射后肺组织中HIF1α活性的触发信号，与辐射诱导的炎症、血管生成和纤维化有关。
To investigate the relationship of HIF1α signaling to oxidative stress, tissue hypoxia, angiogenesis and inflammation, female Fischer 344 rats were irradiated to the right hemithorax with a fractionated dose of 40 Gy (8 Gy × 5 days). The lung tissues were harvested before and at 4, 6, 10, 14, 18, 22 and 26 weeks after irradiation for serial studies of biological markers, including markers for hypoxia (HIF1α, pimonidazole and CA IX), oxidative stress (8-OHdG), and angiogenesis/capillary proliferation (VEGF/CD 105), as well as macrophage activation (ED-1) and cell signaling/fibrosis (NFκB, TGFβ1), using immunohistochemistry and Western blot analysis. HIF1α staining could be observed as early as 4 weeks postirradiation and was significantly increased with time after irradiation. Importantly, HIF1α levels paralleled oxidative stress (8-OHdG), tissue hypoxia (pimonidazole and CA IX), and macrophage accumulation consistent with inflammatory response. Moreover, changes in HIF1α expression identified by immunohistochemistry assay parallel the changes in TGFβ1, VEGF, NFκB and CD 105 levels in irradiated lungs. These results support the notion that oxidative stress and tissue hypoxia might serve as triggering signals for HIF1α activity in irradiated lungs, relating to radiation-induced inflammation, angiogenesis and fibrosis.