Song S, Hua Y, Keep R F, He Y, Wang J, Wu J, Xi G
Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109-2200, USA.
Acta Neurochir Suppl. 2008;105:13-8. doi: 10.1007/978-3-211-09469-3_3.
In this study, we examine the effects of deferoxamine on hemoglobin-induced brain swelling in a newly developed hippocampal model of intracerebral hemorrhage (ICH). There were 2 parts to the experiments in this study. In the first part, male Sprague-Dawley rats received a 10-microL infusion of either packed red blood cells (RBC), lysed RBC, hemoglobin, ferrous iron, or saline, into the hippocampus. In the second part, rats received a 10-microL infusion of hemoglobin and then were treated with either deferoxamine (100 mg/kg, intraperitoneally, given immediately after hemoglobin injection, then every 12h for 24h) or vehicle. Rats were then killed to obtain hippocampus size and DNA damage measurements. We found that lysed RBC induced marked brain swelling in the hippocampus. Compared to saline, hemoglobin or iron injection caused swelling. Systemic use of deferoxamine reduced hemoglobin-induced brain swelling (6.14 +/- 0.45 vs. 7.11 +/- 0.58 mm2 in the vehicle group, p < 0.05). In addition, deferoxamine reduced hemoglobin-induced DNA damage. These results indicate that iron has a key role in hemoglobin-induced brain swelling. Deferoxamine may be a useful treatment for ICH patients.
在本研究中，我们在新建立的脑出血（ICH）海马模型中研究了去铁胺对血红蛋白诱导的脑肿胀的影响。本研究的实验分为两部分。在第一部分中，雄性Sprague-Dawley大鼠海马内分别注入10微升浓缩红细胞（RBC）、裂解的RBC、血红蛋白、亚铁离子或生理盐水。在第二部分中，大鼠海马内注入10微升血红蛋白，然后分别用去铁胺（100毫克/千克，腹腔注射，在注射血红蛋白后立即给药，然后每12小时给药一次，共24小时）或赋形剂治疗。随后处死大鼠以测量海马大小和DNA损伤情况。我们发现裂解的RBC可诱导海马明显的脑肿胀。与生理盐水相比，注射血红蛋白或铁可导致肿胀。全身使用去铁胺可减轻血红蛋白诱导的脑肿胀（赋形剂组为7.11±0.58平方毫米，去铁胺组为6.14±0.45平方毫米，p<0.05）。此外，去铁胺可减轻血红蛋白诱导的DNA损伤。这些结果表明铁在血红蛋白诱导的脑肿胀中起关键作用。去铁胺可能是治疗ICH患者的一种有效药物。
