Iron and iron-handling proteins in the brain after intracerebral hemorrhage
Iron and iron-handling proteins in the brain after intracerebral hemorrhage
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DOI：
10.1161/01.str.0000103140.52838.45
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发表时间：
2003-12-01
期刊：
影响因子：
8.3
通讯作者：
Xi, GH
中科院分区：
文献类型：
--
作者：
Wu, JM;Hua, Y;Xi, GH
背景和目的：有证据表明，脑出血后的脑损伤部分是由于血红蛋白中铁的释放。因此，我们研究了这些铁是否从大脑中清除，以及脑出血对可能改变铁释放或处理的蛋白质的影响：脑血红素加氧酶-1、转铁蛋白、转铁蛋白受体和铁蛋白。方法雄性Sprague-Dawley大鼠分别于1、3、7、14、28 d后向右侧基底节灌注100 μ l自体全血处死。采用增强Perl反应进行铁染色，测定脑内非血红素铁含量。采用Western blot和免疫组化方法检测脑血红素加氧酶-1、转铁蛋白、转铁蛋白受体和铁蛋白。采用免疫荧光双标记法鉴定表达铁蛋白的细胞类型。结果：ich上调血红素氧化酶-1水平，导致脑内铁超载。脑内非血红素铁的显著增加在4周内未被清除。脑转铁蛋白和转铁蛋白受体水平也有所升高。此外，ICH对铁蛋白的上调持续时间很长。结论：脑出血后脑内铁超载和铁处理蛋白（包括转铁蛋白、转铁蛋白受体和铁蛋白）的上调提示铁可能是脑出血治疗的靶点。
Background and Purpose-Evidence indicates that brain injury after intracerebral hemorrhage (ICH) is due in part to the release of iron from hemoglobin. Therefore, we examined whether such iron is cleared from the brain and the effects of ICH on proteins that may alter iron release or handling: brain heme oxygenase-1, transferrin, transferrin receptor, and ferritin.Methods-Male Sprague-Dawley rats received an infusion of 100 muL autologous whole blood into the right basal ganglia and were killed 1, 3, 7, 14, or 28 days later. Enhanced Perl's reaction was used for iron staining, and brain nonheme iron content was determined. Brain heme oxygenase-1, transferrin, transferrin receptor, and ferritin were examined by Western blot analysis and immunohistochemistry. Immunofluorescent double labeling was performed to identify which cell types express ferritin.Results-ICH upregulated heme oxygenase-1 levels and resulted in iron overload in the brain. A marked increase in brain nonheme iron was not cleared within 4 weeks. Brain transferrin and transferrin receptor levels were also increased. In addition, an upregulation of ICH on ferritin was of very long duration.Conclusions-The iron overload and upregulation of iron-handling proteins, including transferrin, transferrin receptor, and ferritin, in the brain after ICH suggest that iron could be a target for ICH therapy.