Zhao Fan, Song Shuijiang, Liu Wenquan, Keep Richard F, Xi Guohua, Hua Ya
Department of Neurosurgery, University of Michigan, Ann Arbor, MI 48109-2200, USA.
Acta Neurochir Suppl. 2011;111:101-5. doi: 10.1007/978-3-7091-0693-8_16.
Red blood cell (RBC) lysis and iron release contribute to intracerebral hemorrhage (ICH)-induced brain injury. Tissue-type transglutaminase (tTG), which has a role in neurodegeneration, is upregulated after ICH. The current study investigated the effect of RBC lysis and iron release on brain tTG levels and neuronal death in a rat model of ICH. This study had three parts: (1) Male Sprague-Dawley rats received an intrahippocampal injection of 10 μL of either packed RBCs or lysed RBCs; (2) rats had a 10 μL injection of either saline, hemoglobin or FeCl2; (3) rats received a 10 μL injection of hemoglobin and were treated with an iron chelator, deferoxamine or vehicle. All rats were killed 24 h later, and the brains were sectioned for tTG and Fluoro-Jade C staining. Lysed but not packed RBCs caused marked tTG upregulation (p<0.05) and neuronal death (p<0.05) in the ipsilateral hippocampus CA-1 region. Both hemoglobin and iron mimicked the effects of lysed RBCs, resulting in tTG expression and neuronal death (p<0.05). Hemoglobin-induced tTG upreglution and neuronal death were reduced by deferoxamine (p<0.05). These results indicate that RBC lysis and iron toxicity contribute to neurodegeneration after ICH.
红细胞（RBC）裂解和铁释放会导致脑出血（ICH）引发的脑损伤。在神经退行性变中起作用的组织型转谷氨酰胺酶（tTG）在脑出血后上调。本研究在脑出血大鼠模型中探究了红细胞裂解和铁释放对脑tTG水平及神经元死亡的影响。本研究分为三个部分：（1）雄性Sprague-Dawley大鼠接受海马内注射10 μL浓缩红细胞或裂解红细胞；（2）大鼠接受10 μL生理盐水、血红蛋白或FeCl2注射；（3）大鼠接受10 μL血红蛋白注射，并接受铁螯合剂去铁胺或载体处理。24小时后处死所有大鼠，取脑切片进行tTG和氟玉髓C染色。裂解而非浓缩红细胞导致同侧海马CA-1区tTG显著上调（p<0.05）和神经元死亡（p<0.05）。血红蛋白和铁均模拟了裂解红细胞的作用，导致tTG表达和神经元死亡（p<0.05）。去铁胺可减轻血红蛋白诱导的tTG上调和神经元死亡（p<0.05）。这些结果表明，红细胞裂解和铁毒性会导致脑出血后的神经退行性变。
