血红素加氧酶-1会加重脑出血后的早期脑损伤。
Heme oxygenase-1 exacerbates early brain injury after intracerebral haemorrhage.
作者信息
Wang Jian, Doré Sylvain
机构信息
Department of Anesthesiology/Critical Care Medicine, Johns Hopkins University, School of Medicine, 720 Rutland Ave, Traylor Bldg 809, Baltimore, MD 21205, USA.
出版信息
Brain. 2007 Jun;130(Pt 6):1643-52. doi: 10.1093/brain/awm095.
Abstract
Because heme oxygenase (HO) is the rate limiting enzyme in the degradation of the pro-oxidant hemin/heme from blood, here we investigated the contribution of the inducible HO-1 to early brain injury produced by intracerebral haemorrhage (ICH). We found that after induction of ICH, HO-1 proteins were highly detectable in the peri-ICH region predominantly in microglia/macrophages and endothelial cells. Remarkably, the injury volume was significantly smaller in HO-1 knockout (HO-1-/-) mice than in wild-type controls 24 and 72 h after ICH. Although the brain water content did not appear to be significantly different, the protection in HO-1-/- mice was associated with a marked reduction in ICH-induced leucocyte infiltration, microglia/macrophage activation and free radical levels. These data reveal a previously unrecognized role of HO-1 in early brain injury after ICH. Thus, modulation of HO-1 signalling should be assessed further in clinical settings, especially for haemorrhagic states.
摘要
由于血红素加氧酶（HO）是血液中促氧化剂血红素/高铁血红素降解过程中的限速酶，我们在此研究了诱导型HO-1在脑出血（ICH）所致早期脑损伤中的作用。我们发现，诱导ICH后，在ICH周边区域可高度检测到HO-1蛋白，主要存在于小胶质细胞/巨噬细胞和内皮细胞中。值得注意的是，ICH后24小时和72小时，HO-1基因敲除（HO-1-/-）小鼠的损伤体积明显小于野生型对照小鼠。尽管脑含水量似乎没有显著差异，但HO-1-/-小鼠受到的保护与ICH诱导的白细胞浸润、小胶质细胞/巨噬细胞激活和自由基水平的显著降低有关。这些数据揭示了HO-1在ICH后早期脑损伤中以前未被认识的作用。因此，应在临床环境中进一步评估HO-1信号通路的调节作用，特别是对于出血性疾病。
相似文献
1
Heme oxygenase-1 exacerbates early brain injury after intracerebral haemorrhage.血红素加氧酶-1会加重脑出血后的早期脑损伤。
Brain. 2007 Jun;130(Pt 6):1643-52. doi: 10.1093/brain/awm095.
2
Microglial FoxO3a deficiency ameliorates ferroptosis-induced brain injury of intracerebral haemorrhage via regulating autophagy and heme oxygenase-1.小胶质细胞 FoxO3a 缺乏通过调节自噬和血红素加氧酶-1减轻脑出血诱导的铁死亡性脑损伤。
J Cell Mol Med. 2024 Jan;28(1):e18007. doi: 10.1111/jcmm.18007. Epub 2023 Oct 27.
3
Neuroprotection of Heme Oxygenase-2 in Mice AfterIntracerebral Hemorrhage.血红素加氧酶-2 对脑出血后小鼠的神经保护作用。
J Neuropathol Exp Neurol. 2021 Apr 16;80(5):457-466. doi: 10.1093/jnen/nlab025.
4
Microglial HO-1 aggravates neuronal ferroptosis via regulating iron metabolism and inflammation in the early stage after intracerebral hemorrhage.小胶质细胞血红素加氧酶-1通过调节脑出血后早期的铁代谢和炎症反应加重神经元铁死亡。
Int Immunopharmacol. 2025 Feb 6;147:113942. doi: 10.1016/j.intimp.2024.113942. Epub 2024 Dec 30.
5
Attenuation of oxidative injury after induction of experimental intracerebral hemorrhage in heme oxygenase-2 knockout mice.血红素加氧酶-2基因敲除小鼠实验性脑出血诱导后氧化损伤的减轻
J Neurosurg. 2007 Mar;106(3):428-35. doi: 10.3171/jns.2007.106.3.428.
6
Distinct role of heme oxygenase-1 in early- and late-stage intracerebral hemorrhage in 12-month-old mice.血红素加氧酶-1在12月龄小鼠早期和晚期脑出血中的不同作用。
J Cereb Blood Flow Metab. 2017 Jan;37(1):25-38. doi: 10.1177/0271678X16655814. Epub 2016 Jun 17.
7
A novel Nrf2 activator, RS9, attenuates secondary brain injury after intracerebral hemorrhage in sub-acute phase.一种新型 Nrf2 激活剂 RS9 可减轻亚急性期脑出血后的二次脑损伤。
Brain Res. 2018 Dec 15;1701:137-145. doi: 10.1016/j.brainres.2018.08.021. Epub 2018 Aug 22.
8
HO-1 represses NF-κB signaling pathway to mediate microglia polarization and phagocytosis in intracerebral hemorrhage.血红素加氧酶-1抑制核因子κB信号通路，介导脑出血中微胶质细胞极化和吞噬作用。
Neuroscience. 2025 Feb 6;566:17-27. doi: 10.1016/j.neuroscience.2024.12.020. Epub 2024 Dec 11.
9
Heme oxygenase 2 deficiency increases brain swelling and inflammation after intracerebral hemorrhage.血红素加氧酶2缺乏会增加脑出血后的脑肿胀和炎症。
Neuroscience. 2008 Sep 9;155(4):1133-41. doi: 10.1016/j.neuroscience.2008.07.004. Epub 2008 Jul 8.
10
Time course of Keap1-Nrf2 pathway expression after experimental intracerebral haemorrhage: correlation with brain oedema and neurological deficit.实验性脑出血后 Keap1-Nrf2 通路表达的时程：与脑水肿和神经功能缺损的相关性。
Free Radic Res. 2013 May;47(5):368-75. doi: 10.3109/10715762.2013.778403. Epub 2013 Mar 21.
引用本文的文献
1
HCAR2 is a novel receptor for heme.HCAR2是一种新型的血红素受体。
Blood Adv. 2025 Sep 9;9(17):4458-4469. doi: 10.1182/bloodadvances.2025016197.
2
Natural flavonoids from herbs and nutraceuticals as ferroptosis inhibitors in central nervous system diseases: current preclinical evidence and future perspectives.草药和营养保健品中的天然黄酮类化合物作为中枢神经系统疾病中的铁死亡抑制剂：当前的临床前证据及未来展望
Front Pharmacol. 2025 Mar 24;16:1570069. doi: 10.3389/fphar.2025.1570069. eCollection 2025.
3
Intracerebral Hemorrhage-Associated Iron Release Leads to Pericyte-Dependent Cerebral Capillary Function Disruption.脑出血相关的铁释放导致周细胞依赖性脑毛细血管功能破坏。
Biomolecules. 2025 Jan 22;15(2):164. doi: 10.3390/biom15020164.
4
NLRP3 inflammasome and gut microbiota-brain axis: a new perspective on white matter injury after intracerebral hemorrhage.NLRP3炎性小体与肠道微生物群-脑轴：脑出血后白质损伤的新视角
Neural Regen Res. 2025 Jan 29;21(1):62-80. doi: 10.4103/NRR.NRR-D-24-00917.
5
Pharmacological Effects of Antioxidant Mycosporine-Glycine in Alleviating Ultraviolet B-Induced Skin Photodamage: Insights from Metabolomic and Transcriptomic Analyses.抗氧化剂肌孢素-甘氨酸减轻紫外线B诱导的皮肤光损伤的药理作用：代谢组学和转录组学分析的见解
Antioxidants (Basel). 2024 Dec 29;14(1):30. doi: 10.3390/antiox14010030.
6
Neuroprotective effects of baicalin and baicalein on the central nervous system and the underlying mechanisms.黄芩苷和黄芩素对中枢神经系统的神经保护作用及其潜在机制。
Heliyon. 2024 Dec 10;11(1):e41002. doi: 10.1016/j.heliyon.2024.e41002. eCollection 2025 Jan 15.
7
A dispensable role of mural cell-derived laminin-5 in intracerebral hemorrhage.壁细胞衍生层粘连蛋白-5在脑出血中的可有可无的作用。
J Cereb Blood Flow Metab. 2024 Sep;44(9):1677-1690. doi: 10.1177/0271678X241264083. Epub 2024 Jul 25.
8
Menaquinone-4 Alleviates Neurological Deficits Associated with Intracerebral Hemorrhage by Preserving Corticospinal Tract in Mice.甲萘醌-4 通过保护小鼠皮质脊髓束减轻脑出血相关的神经功能缺损。
Neurochem Res. 2024 Jul;49(7):1838-1850. doi: 10.1007/s11064-024-04150-8. Epub 2024 May 10.
9
Modulation of GPER1 alleviates early brain injury via inhibition of A1 reactive astrocytes activation after intracerebral hemorrhage in mice.在小鼠脑出血后，通过抑制A1反应性星形胶质细胞的激活，GPER1的调节可减轻早期脑损伤。
Heliyon. 2024 Feb 25;10(5):e26909. doi: 10.1016/j.heliyon.2024.e26909. eCollection 2024 Mar 15.
10
Iron homeostasis and post-hemorrhagic hydrocephalus: a review.铁稳态与出血后脑积水：综述
Front Neurol. 2024 Jan 12;14:1287559. doi: 10.3389/fneur.2023.1287559. eCollection 2023.
本文引用的文献
1
Inflammation after intracerebral hemorrhage.脑出血后的炎症反应。
J Cereb Blood Flow Metab. 2007 May;27(5):894-908. doi: 10.1038/sj.jcbfm.9600403. Epub 2006 Oct 11.
2
Astrocytic induction of matrix metalloproteinase-9 and edema in brain hemorrhage.星形胶质细胞诱导脑出血中基质金属蛋白酶-9及水肿的产生
J Cereb Blood Flow Metab. 2007 Mar;27(3):460-8. doi: 10.1038/sj.jcbfm.9600354. Epub 2006 Jun 21.
3
Latest advances in intracerebral hemorrhage.
Curr Neurol Neurosci Rep. 2006 Jan;6(1):17-22. doi: 10.1007/s11910-996-0004-0.
4
Products of heme oxygenase and their potential therapeutic applications.血红素加氧酶的产物及其潜在的治疗应用。
Am J Physiol Renal Physiol. 2006 Mar;290(3):F563-71. doi: 10.1152/ajprenal.00220.2005.
5
Heme oxygenase 2 is neuroprotective against intracerebral hemorrhage.血红素加氧酶2对脑出血具有神经保护作用。
Neurobiol Dis. 2006 Jun;22(3):473-6. doi: 10.1016/j.nbd.2005.12.009. Epub 2006 Feb 3.
6
Protective effects of nicergoline against neuronal cell death induced by activated microglia and astrocytes.尼麦角林对活化小胶质细胞和星形胶质细胞诱导的神经元细胞死亡的保护作用。
Brain Res. 2005 Dec 20;1066(1-2):78-85. doi: 10.1016/j.brainres.2005.10.050. Epub 2005 Dec 1.
7
Contribution of extracellular proteolysis and microglia to intracerebral hemorrhage.细胞外蛋白水解和小胶质细胞在脑出血中的作用。
Neurocrit Care. 2005;3(1):77-85. doi: 10.1385/NCC:3:1:077.
8
The deleterious or beneficial effects of different agents in intracerebral hemorrhage: think big, think small, or is hematoma size important?不同药物在脑出血中的有害或有益作用：从大处着眼，从小处着手，还是血肿大小很重要？
Stroke. 2005 Jul;36(7):1594-6. doi: 10.1161/01.STR.0000170701.41507.e1. Epub 2005 Jun 2.
9
Regulation of microglial behavior by ion channel activity.离子通道活性对小胶质细胞行为的调节
J Neurosci Res. 2005 Aug 1;81(3):314-21. doi: 10.1002/jnr.20476.
10
New horizons for primary intracerebral hemorrhage treatment: experience from preclinical studies.原发性脑出血治疗的新视野：来自临床前研究的经验
Neurol Res. 2005 Apr;27(3):268-79. doi: 10.1179/016164105X25225.
Zotero 插件