血红素加氧酶2对脑出血具有神经保护作用。

Heme oxygenase 2 is neuroprotective against intracerebral hemorrhage.

作者信息

Wang Jian, Zhuang Hean, Doré Sylvain

机构信息

Department of Anesthesiology/Critical Care Medicine, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross Bldg. 364-365, Baltimore, MD 21205, USA.

出版信息

Neurobiol Dis. 2006 Jun;22(3):473-6. doi: 10.1016/j.nbd.2005.12.009. Epub 2006 Feb 3.

DOI:10.1016/j.nbd.2005.12.009

PMID:16459095

Abstract

Recent studies suggest a neuroprotective function for heme oxygenase 2 (HO2) in acute brain injury and ischemia. HO2, the main enzyme to degrade the pro-oxidant heme, was tested for its neuroprotective ability in postnatal neuronal cell cultures and in a model of collagenase-induced intracerebral hemorrhage. Genetic deletion of HO2 rendered cultured neurons 32% (P < 0.01) more vulnerable to hemin-induced toxicity, increased brain injury volume in mice by 30% (P < 0.05) at day 1 and by 67% (P < 0.05) at day 3, and worsened neurologic functions by 26% (P < 0.05) at day 1 and by 38% (P < 0.05) at day 3 following exposure to free heme liberated from hemorrhage. Together, these findings suggest that HO2 is a crucial neuroprotective enzyme in detoxifying high levels of heme from the brain and that further work is warranted to investigate potential therapeutic strategies that target HO2 in intracerebral hemorrhage.

摘要

最近的研究表明，血红素加氧酶2（HO2）在急性脑损伤和缺血中具有神经保护功能。HO2是降解促氧化血红素的主要酶，已在产后神经元细胞培养物和胶原酶诱导的脑出血模型中测试了其神经保护能力。HO2基因缺失使培养的神经元对血红素诱导的毒性更敏感（增加32%，P < 0.01），在第1天使小鼠脑损伤体积增加30%（P < 0.05），在第3天增加67%（P < 0.05），并且在暴露于出血释放的游离血红素后，第1天神经功能恶化26%（P < 0.05），第3天恶化38%（P < 0.05）。这些研究结果共同表明，HO2是一种关键的神经保护酶，可将大脑中高水平的血红素解毒，并且有必要进一步开展工作，以研究针对脑出血中HO2的潜在治疗策略。