Hypoxia and hypoxia-inducible factor in the burn wound.

Hypoxia and hypoxia-inducible factor in the burn wound.
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烧伤伤口中缺氧和缺氧诱导因子。

DOI:
10.1111/j.1524-475x.2010.00656.x
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发表时间:
2011-03
期刊:
Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society
影响因子:
--
通讯作者:
Harmon JW
Harmon JW
中科院分区:
其他
文献类型:
--
作者:
Xing D;Liu L;Marti GP;Zhang X;Reinblatt M;Milner SM;Harmon JW

文献摘要

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缺氧诱导因子(HIF)在伤口愈合过程中促进血管生成和血管生成的重要性已得到证实。人们普遍认为,HIF活性可由多种因素促进,包括伤口缺氧或炎症细胞浸润创面产生的细胞因子。然而,对于烧伤创面HIF活性与缺氧之间的关系,目前还没有系统的探讨。缺氧组织的位置尚未明确。缺氧的出现和HIF活性的增加以及HIF下游转录产物的出现的时间过程尚未描述。本研究的目的是利用吡咪唑(一种特殊的组织缺氧标志物)表征小鼠烧伤模型中缺氧的时空过程,并将其与HIF-1α及其重要的血管生成和血管生成转录产物VEGF和SDF-1的出现联系起来。烧伤创面愈合缘缺氧开始于烧伤后48小时,在烧伤后第3天达到高峰。在同一组织块的连续切片上,HIF-1α、SDF-1和VEGF的阳性染色均出现在愈合区的前缘,并在第3天达到峰值,缺氧也是如此。采用免疫组化分析探讨创面缺氧区特征。发现缺氧的局部化与细胞生长和迁移有关,而与增殖或炎症浸润无关。
The importance of hypoxia-inducible factor (HIF) in promoting angiogenesis and vasculogenesis during wound healing has been demonstrated. It is widely accepted that HIF activity can be promoted by many factors, including hypoxia in the wound or cytokines from inflammatory cells infiltrating the wound. However, there has not been a systematic exploration of the relationship between HIF activity and hypoxia in the burn wound. The location of the hypoxic tissue has not been clearly delineated. The time course of the appearance of hypoxia and the increased activity of HIF and appearance of HIF’s downstream transcription products has not been described. The aim of this study was to utilize pimonidazole, a specific tissue hypoxia marker, to characterize the spatial and temporal course of hypoxia in a murine burn model and correlate this with the appearance of HIF-1α and its important angiogenic and vasculogenic transcription products VEGF and SDF-1. Hypoxia was found in the healing margin of burn wounds beginning at 48 hours after burn and peaking at day 3 after burn. On sequential sections of the same tissue block, positive staining of HIF-1α, SDF-1, and VEGF all occurred at the leading margin of the healing area and peaked at day 3, as did hypoxia. Immunohistochemical analysis was used to explore the characteristics of the hypoxic region of the wound. The localization of hypoxia was found to be related to cell growth and migration, but not to proliferation or inflammatory infiltration.