Early wound healing exhibits cytokine surge without evidence of hypoxia
Early wound healing exhibits cytokine surge without evidence of hypoxia
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DOI：
10.1097/00000658-200001000-00020
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发表时间：
2000-01-01
影响因子：
9
通讯作者：
Dewhirst, MW
中科院分区：
文献类型：
--
作者：
Haroon, ZA;Raleigh, JA;Dewhirst, MW
目的
确定伤口缺氧与所涉及的细胞类型、特定血管生成细胞因子的表达、伤口部位细胞的增殖状态以及血管生成在空间和时间上的关系。
总结背景资料
缺氧被认为是通过上调在伤口愈合过程中观察到的血管生成细胞因子来驱动血管生成反应。但是由于在细胞水平测量组织氧分压存在局限性，这种相关性尚未在体内细胞对细胞的基础上得到证实。
方法
以大鼠穿孔活检伤口作为伤口愈合模型，在愈合过程中通过免疫组织化学方法追踪血管内皮生长因子、转化生长因子 -β、肿瘤坏死因子 -α和吡莫硝唑加合物（作为缺氧标记物）的分布。
结果
受伤后第1天不存在缺氧，尽管在伤口中观察到血管生成和细胞因子的最大表达。缺氧在第4天的肉芽组织阶段达到峰值，并与细胞数量增加和细胞增殖相关。缺氧在第4天后开始下降，并局限于瘢痕组织中的残留血管和上皮层。
结论
在伤口愈合早期血管生成细胞因子的诱导可能是由于缺氧以外的触发机制。或者，随着伤口细胞数量和增殖的消退，细胞缺氧发展和下降的独特模式表明它参与了愈合后期血管退化的启动。
ObjectiveTo ascertain the spatial and temporal relation of wound hypoxia to the cell types involved, expression of selected angiogenic cytokines, the proliferative status of cells in the wound site, and angiogenesis.Summary Background DataHypoxia is considered to drive the angiogenic response by upregulating angiogenic cytokines observed during wound healing. But this correlation has not been shown on a cell-to cell basis in vivo because of limitations in measuring tissue Po-2 at the cellular level.MethodsUsing punch biopsy wounds in rats as a wound healing model, the distributions of vascular endothelial growth factor, transforming growth factor-beta, tumor necrosis factor-alpha, and pimonidazole adducts (as a hypoxia marker) were followed immunohistochemically during the healing process.ResultsHypoxia was absent on day 1 after wounding, even though angiogenesis and maximal expression of cytokines were observed in the wounds. Hypoxia peaked in the granulation tissue stage at day 4 and correlated with increased cellularity and cellular proliferation. Hypoxia started to decrease after day 4 and was limited to the remnant blood vessels and epithelial layer in the scar tissue.ConclusionsInduction of angiogenic cytokines early during wound healing may be due to triggering mechanisms other than hypoxia. Alternatively, the unique pattern of development and decline of cellular hypoxia as wound cellularity and proliferation regress suggest its involvement in initiating vascular regression during the later stages of healing.