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从金属金颗粒中生物释放的金离子可减轻局灶性脑损伤中的炎症和细胞凋亡,并增强再生反应。

Gold ions bio-released from metallic gold particles reduce inflammation and apoptosis and increase the regenerative responses in focal brain injury.

作者信息

Larsen Agnete, Kolind Kristian, Pedersen Dan Sonne, Doering Peter, Pedersen Mie Ostergaard, Danscher Gorm, Penkowa Milena, Stoltenberg Meredin

机构信息

Department of Neurobiology, Institute of Anatomy, University of Aarhus, 8000 Aarhus C, Denmark.

出版信息

Histochem Cell Biol. 2008 Oct;130(4):681-92. doi: 10.1007/s00418-008-0448-1. Epub 2008 Jun 10.

Abstract

Traumatic brain injury results in loss of neurons caused as much by the resulting neuroinflammation as by the injury. Gold salts are known to be immunosuppressive, but their use are limited by nephrotoxicity. However, as we have proven that implants of pure metallic gold release gold ions which do not spread in the body, but are taken up by cells near the implant, we hypothesize that metallic gold could reduce local neuroinflammation in a safe way. Bio-liberation, or dissolucytosis, of gold ions from metallic gold surfaces requires the presence of disolycytes i.e. macrophages and the process is limited by their number and activity. We injected 20-45 mum gold particles into the neocortex of mice before generating a cryo-injury. Comparing gold-treated and untreated cryolesions, the release of gold reduced microgliosis and neuronal apoptosis accompanied by a transient astrogliosis and an increased neural stem cell response. We conclude that bio-liberated gold ions possess pronounced anti-inflammatory and neuron-protective capacities in the brain and suggest that metallic gold has clinical potentials. Intra-cerebral application of metallic gold as a pharmaceutical source of gold ions represents a completely new medical concept that bypasses the blood-brain-barrier and allows direct drug delivery to inflamed brain tissue.

摘要

创伤性脑损伤导致的神经元丧失,其造成的原因与损伤本身一样多,也与由此引发的神经炎症有关。已知金盐具有免疫抑制作用,但其使用因肾毒性而受到限制。然而,正如我们所证明的,纯金属金植入物会释放金离子,这些金离子不会在体内扩散,而是被植入物附近的细胞摄取,我们推测金属金可以以安全的方式减轻局部神经炎症。金离子从金属金表面的生物释放,即溶解细胞作用,需要溶解细胞的存在,即巨噬细胞,并且该过程受其数量和活性的限制。在造成冷冻损伤之前,我们将20 - 45微米的金颗粒注入小鼠的新皮层。比较经金处理和未经处理的冷冻损伤,金的释放减少了小胶质细胞增生和神经元凋亡,同时伴有短暂的星形胶质细胞增生和神经干细胞反应增加。我们得出结论,生物释放的金离子在大脑中具有显著的抗炎和神经保护能力,并表明金属金具有临床潜力。将金属金作为金离子的药物来源进行脑内应用代表了一种全新的医学概念,它绕过血脑屏障,允许直接将药物递送至炎症性脑组织。

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