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Association between haptoglobin, hemopexin and mortality in adults with sepsis.成人脓毒症患者中触珠蛋白、血红素结合蛋白与死亡率之间的关联。
Crit Care. 2013 Nov 14;17(6):R272. doi: 10.1186/cc13108.
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The intrathecal CD163-haptoglobin-hemoglobin scavenging system in subarachnoid hemorrhage.蛛网膜下腔出血中的鞘内 CD163-触珠蛋白-血红蛋白清除系统。
J Neurochem. 2012 Jun;121(5):785-92. doi: 10.1111/j.1471-4159.2012.07716.x. Epub 2012 Mar 30.
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Increased striatal injury and behavioral deficits after intracerebral hemorrhage in hemopexin knockout mice.载脂蛋白缺失小鼠脑出血后纹状体损伤增加和行为缺陷。
J Neurosurg. 2011 Apr;114(4):1159-67. doi: 10.3171/2010.10.JNS10861. Epub 2010 Dec 3.
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A central role for free heme in the pathogenesis of severe sepsis.游离血红素在严重脓毒症发病机制中的核心作用。
Sci Transl Med. 2010 Sep 29;2(51):51ra71. doi: 10.1126/scitranslmed.3001118.
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Heme impairs prostaglandin E2 and TGF-beta production by human mononuclear cells via Cu/Zn superoxide dismutase: insight into the pathogenesis of severe malaria.血红素通过铜/锌超氧化物歧化酶抑制人单核细胞产生前列腺素 E2 和转化生长因子-β:严重疟疾发病机制的新见解。
J Immunol. 2010 Jul 15;185(2):1196-204. doi: 10.4049/jimmunol.0904179. Epub 2010 Jun 18.
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High ICP as trigger of proinflammatory IL-6 cytokine activation in aneurysmal subarachnoid hemorrhage.高颅内压作为动脉瘤性蛛网膜下腔出血中促炎细胞因子白细胞介素-6激活的触发因素。
Neurol Res. 2010 Sep;32(7):728-35. doi: 10.1179/016164109X12464612122650. Epub 2009 Aug 13.
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Elevated metals compromise repair of oxidative DNA damage via the base excision repair pathway: implications of pathologic iron overload in the brain on integrity of neuronal DNA.金属含量升高会通过碱基切除修复途径损害氧化性DNA损伤的修复:脑内病理性铁过载对神经元DNA完整性的影响。
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On the fate of extracellular hemoglobin and heme in brain.关于脑内细胞外血红蛋白和血红素的命运
J Cereb Blood Flow Metab. 2009 Jun;29(6):1109-20. doi: 10.1038/jcbfm.2009.34. Epub 2009 Apr 1.
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Relationship between sympathetic nervous activity and inflammatory response after subarachnoid hemorrhage in a perforating canine model.穿孔性犬模型蛛网膜下腔出血后交感神经活动与炎症反应的关系
Auton Neurosci. 2009 May 11;147(1-2):70-4. doi: 10.1016/j.autneu.2009.01.010. Epub 2009 Feb 13.
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Iron is a potential key mediator of glutamate excitotoxicity in spinal cord motor neurons.
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血红蛋白代谢产物与出血性脑卒中患者的炎症反应相关。

Hemoglobin metabolism by-products are associated with an inflammatory response in patients with hemorrhagic stroke.

作者信息

Righy Cássia, Turon Ricardo, Freitas Gabriel de, Japiassú André Miguel, Faria Neto Hugo Caire de Castro, Bozza Marcelo, Oliveira Marcus F, Bozza Fernando A

机构信息

Laboratório de Pesquisa Clínica em Medicina Intensiva, Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil.

Instituto Estadual do Cérebro Paulo Niemeyer, Rio de Janeiro, RJ, Brasil.

出版信息

Rev Bras Ter Intensiva. 2018 Mar;30(1):21-27. doi: 10.5935/0103-507x.20180003. Epub 2018 Mar 15.

DOI:10.5935/0103-507x.20180003
PMID:29742229
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5885227/
Abstract

OBJECTIVE

To evaluate the relationships of brain iron and heme with the inflammatory response of the systemic and central nervous systems and to investigate the role of defensive systems against the toxicity of iron and heme in the central nervous system.

METHODS

We assessed a prospective cohort of patients presenting with intracerebral and subarachnoid hemorrhage. We assayed plasma and cerebrospinal fluid samples for the presence of iron, heme, hemopexin, haptoglobin, enolase, S100-β and cytokines for the first three days following hemorrhagic stroke. We also analyzed the dynamic changes in these components within both fluids and their relationship with early mortality rates.

RESULTS

Hemopexin and haptoglobin concentrations were nearly negligible in the brain after intracerebral and subarachnoid hemorrhage. Cerebrospinal fluid iron and heme concentrations correlated with a pro-inflammatory response in the central nervous system, and plasmatic and cerebrospinal fluid inflammatory profiles on the third day after hemorrhagic stroke were related to early mortality rates. Interleukin 4 levels within the cerebrospinal fluid during the first 24 hours after hemorrhagic stroke were found to be higher in survivors than in non-survivors.

CONCLUSION

Iron and heme are associated with a pro-inflammatory response in the central nervous system following hemorrhagic stroke, and protections against hemoglobin and heme are lacking within the human brain. Patient inflammatory profiles were associated with a poorer prognosis, and local anti-inflammatory responses appeared to have a protective role.

摘要

目的

评估脑铁和血红素与全身及中枢神经系统炎症反应的关系,并研究中枢神经系统中铁和血红素毒性防御系统的作用。

方法

我们评估了一组患有脑内出血和蛛网膜下腔出血的前瞻性队列患者。在出血性中风后的头三天,我们检测了血浆和脑脊液样本中的铁、血红素、血红素结合蛋白、触珠蛋白、烯醇化酶、S100-β和细胞因子。我们还分析了这些成分在两种液体中的动态变化及其与早期死亡率的关系。

结果

脑内出血和蛛网膜下腔出血后,脑中血红素结合蛋白和触珠蛋白浓度几乎可以忽略不计。脑脊液中铁和血红素浓度与中枢神经系统的促炎反应相关,出血性中风后第三天的血浆和脑脊液炎症谱与早期死亡率相关。出血性中风后24小时内,幸存者脑脊液中的白细胞介素4水平高于非幸存者。

结论

铁和血红素与出血性中风后中枢神经系统的促炎反应相关,人脑内缺乏针对血红蛋白和血红素的保护机制。患者的炎症谱与较差的预后相关,局部抗炎反应似乎具有保护作用。