Radiation-induced hypoxia may perpetuate late normal tissue injury
Radiation-induced hypoxia may perpetuate late normal tissue injury
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DOI：
10.1016/s0360-3016(01)01593-0
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发表时间：
2001-07-15
影响因子：
7
通讯作者：
Haroon, ZA
中科院分区：
文献类型：
--
作者：
Vujaskovic, Z;Anscher, MS;Haroon, ZA
目的：本研究的目的是确定放射后大鼠肺组织是否发生缺氧。方法与材料：采用Fisher-344大鼠右半胸单次照射，剂量28 Gy。照射后6个月，通过每2周测量呼吸频率的变化来评估肺功能。在安乐死前3小时给予缺氧标记。分别于照射后6周和6个月收获组织，进行免疫组织化学处理。结果：照射后6周，在功能或组织病理改变发生前，大鼠肺部出现中度缺氧。在放疗后较晚的时间点（6个月）发生的更严重的缺氧与巨噬细胞活性、胶原沉积、肺纤维化和呼吸速率升高显著增加相关。免疫组织化学研究显示tgf - β， VEGF和CD-31内皮细胞标志物的增加，提示缺氧介导的原纤维生成和促血管生成途径的激活。结论：一种新的辐射性肺损伤模式应该考虑辐射后缺氧是一个重要的促进因素，介导一系列炎症和纤维化细胞因子的持续产生。(C) 2001爱思唯尔科学公司
Purpose: The purpose of this study was to determine whether or not hypoxia develops in rat lung tissue after radiation.Methods and Materials: Fisher-344 rats were irradiated to the right hemithorax using a single dose of 28 Gy. Pulmonary function was assessed by measuring the changes in respiratory rate every 2 weeks, for 6 months after irradiation. The hypoxia marker was administered 3 h before euthanasia. The tissues were harvested at 6 weeks and 6 months after irradiation and processed for immunohistochemistry.Results: A moderate hypoxia was detected in the rat lungs at 6 weeks after irradiation, before the onset of functional or histopathologic changes. The more severe hypoxia, that developed at the later time points (6 months) after irradiation, was associated with a significant increase in macrophage activity, collagen deposition, lung fibrosis, and elevation in the respiratory rate. Immunohistochemistry studies revealed an increase in TGF-beta, VEGF, and CD-31 endothelial cell marker, suggesting a hypoxia-mediated activation of the profibrinogenic and proangiogenic pathways.Conclusion: A new paradigm of radiation-induced Lung injury should consider postradiation hypoxia to be an important contributing factor mediating a continuous production of a number of inflammatory and fibrogenic cytokines. (C) 2001 Elsevier Science Inc.