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脑出血猪模型中的铁蓄积与DNA损伤

Iron accumulation and DNA damage in a pig model of intracerebral hemorrhage.

作者信息

Gu Yuxiang, Hua Ya, He Yangdong, Wang Lin, Hu Hua, Keep Richard F, Xi Guohua

机构信息

Department of Neurosurgery, University of Michigan, Ann Arbor, MI 48109-2200, USA.

出版信息

Acta Neurochir Suppl. 2011;111:123-8. doi: 10.1007/978-3-7091-0693-8_20.

Abstract

Cerebral iron overload causes brain injury after intracerebral hemorrhage (ICH) in rats and pigs. The current study examined whether an iron chelator, deferoxamine, can reduce ICH-induced DNA damage in pigs. Pigs received an injection of autologous blood into the right frontal lobe. Deferoxamine (50 mg/kg, i.m.) or vehicle was given 2 h after ICH and then every 12 h up to 7 days. Animals were killed at day 3 or day 7 after ICH to examine iron accumulation and DNA damage. We found that ICH resulted in the development of a reddish perihematomal zone, with iron accumulation and DNA damage within that zone. Deferoxamine treatment reduced the perihematomal reddish zone, and the number of Perls' (p<0.01) and TUNEL (p<0.01) positive cells. In conclusion, iron accumulates in the perihematomal zone and causes DNA damage. Systemic deferoxamine treatment reduces ICH-induced iron overload and DNA damage in pigs.

摘要

脑铁过载在大鼠和猪的脑出血(ICH)后会导致脑损伤。本研究检测了铁螯合剂去铁胺是否能减轻猪ICH诱导的DNA损伤。给猪的右额叶注射自体血。脑出血后2小时给予去铁胺(50mg/kg,肌肉注射)或赋形剂,然后每12小时给药一次,持续7天。在脑出血后第3天或第7天处死动物,以检测铁蓄积和DNA损伤。我们发现,脑出血导致血肿周围出现红色区域,该区域有铁蓄积和DNA损伤。去铁胺治疗减少了血肿周围的红色区域以及Perls(p<0.01)和TUNEL(p<0.01)阳性细胞的数量。总之,铁在血肿周围区域蓄积并导致DNA损伤。全身性去铁胺治疗可减轻猪ICH诱导的铁过载和DNA损伤。

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