Center for Wound Healing and Tissue Regeneration, College of Dentistry, University of Illinois at Chicago, 801 S. Paulina St., MC 859, Chicago, IL 60612, USA.
J Dent Res. 2012 Sep;91(9):871-6. doi: 10.1177/0022034512454435. Epub 2012 Jul 19.
Despite accelerated epithelial closure, oral mucosal wounds exhibit lower levels of VEGF and a more refined angiogenic response than do skin wounds. The specific differences in angiogenesis suggest that skin and oral mucosal wounds may experience dissimilar levels of hypoxia and HIF-1α. Using a model of comparable wounds on murine dorsal skin and tongue, we determined levels of hypoxia and HIF-1α. Skin wounds were found to be significantly more hypoxic and had higher levels of HIF-1α than mucosal wounds. Furthermore, under stressed conditions, skin wounds, but not mucosal wounds, exhibited a further elevation of HIF-1α beyond that of non-stressed levels. To determine if manipulation of oxygen levels might equalize the repair response of each tissue, we exposed mice to hyperbaric oxygen treatment (HBOT) following wounding. HBOT did not significantly change HIF-1α or VEGF expression in either skin or mucosal wounds, nor did it alter wound bed vascularity. These studies suggest that skin wounds have higher levels of hypoxia than do mucosal wounds, along with a differential expression of HIF-1α. Interestingly, modulation of oxygen by HBOT does not ameliorate this difference. These results suggest that differential responses to hypoxia may underlie the distinctive wound-healing phenotypes seen in skin and oral mucosa.
尽管上皮细胞的愈合速度加快，但口腔黏膜伤口的血管内皮生长因子 (VEGF) 水平较低，血管生成反应也更为精细，与皮肤伤口相比。血管生成的这些具体差异表明，皮肤和口腔黏膜伤口可能经历不同程度的缺氧和 HIF-1α。我们使用小鼠背部皮肤和舌部类似伤口的模型来确定缺氧和 HIF-1α 的水平。结果发现，皮肤伤口的缺氧程度明显更高，HIF-1α 水平也高于黏膜伤口。此外，在应激条件下，皮肤伤口而非黏膜伤口的 HIF-1α 水平进一步升高，超过了非应激水平。为了确定调节氧气水平是否可以使每种组织的修复反应达到平衡，我们在受伤后对小鼠进行高压氧治疗 (HBOT)。HBOT 治疗并未显著改变皮肤或黏膜伤口中的 HIF-1α 或 VEGF 表达，也未改变伤口床的血管生成。这些研究表明，皮肤伤口的缺氧程度高于黏膜伤口，同时 HIF-1α 的表达也存在差异。有趣的是，HBOT 对氧气的调节并不能改善这种差异。这些结果表明，对缺氧的不同反应可能是皮肤和口腔黏膜伤口愈合表型不同的基础。
