Mogford Jon E, Sisco Mark, Bonomo Steve R, Robinson Alan M, Mustoe Thomas A
Wound Healing Research Laboratory, Division of Plastic and Reconstructive Surgery, Northwestern University, Chicago, Illinois 60611, USA.
J Surg Res. 2004 May 15;118(2):190-6. doi: 10.1016/S0022-4804(03)00349-4.
Tissue ischemia and aging are independent features associated with the healing impairment of cutaneous wounds. However, the pathophysiology of these processes as they relate to impaired-healing wounds is poorly understood.
A single full-thickness biopsy wound was made on both ears of young (3-6 month) and aged (>24 month) Fisher rats. One ear was rendered ischemic by transection of the vasculature at the ear base, while the other ear served as an internal nonischemic control. Wounds were harvested from 3 to 7 days and were evaluated histologically for either granulation tissue formation and epithelialization. Total RNA from wounds harvested at postoperative day 7 was probed using a nylon-based cDNA array to assess global genetic expression alterations.
Healing in the rat ear model is impaired by both ischemia and advanced age as measured by granulation tissue formation and wound epithelialization. Granulation tissue formation was affected to a greater degree by ischemia than age (-58% versus -21%, respectively) while epithelialization displayed an opposite response (-17% versus -53%, respectively). Global analysis of gene expression suggests that ischemia engenders a marked increase in genes displaying altered expression in aged animals compared to young animals. Importantly, all possible alterations in gene expression are found in samples from aged ischemic wounds, indicating that gene regulation is not simply depressed by advanced age.
Wound epithelialization appears to be affected to a greater degree by advanced age than by ischemia. The results demonstrate the distinctive phenotype presented by the clinically relevant combination of age and ischemia in an in vivo model of cutaneous wound healing.
组织缺血和衰老都是与皮肤伤口愈合受损相关的独立特征。然而，这些过程与愈合受损伤口相关的病理生理学仍知之甚少。
在年轻（3 - 6个月）和老年（>24个月）的Fisher大鼠双耳上制作单个全层活检伤口。一只耳朵通过在耳基部横断脉管系统使其缺血，而另一只耳朵作为内部非缺血对照。在3至7天收集伤口，并进行组织学评估以观察肉芽组织形成和上皮化情况。使用基于尼龙的cDNA阵列对术后第7天收集的伤口总RNA进行检测，以评估整体基因表达变化。
通过肉芽组织形成和伤口上皮化测量发现，大鼠耳部模型中的愈合受到缺血和老龄的损害。肉芽组织形成受缺血影响的程度大于年龄（分别为-58%对-21%），而上皮化则呈现相反的反应（分别为-17%对-53%）。基因表达的整体分析表明，与年轻动物相比，缺血导致老年动物中显示表达改变的基因显著增加。重要的是，在老年缺血伤口样本中发现了所有可能的基因表达变化，这表明基因调控并非仅仅因老龄而受到抑制。
伤口上皮化似乎受老龄影响的程度大于缺血。结果表明在皮肤伤口愈合的体内模型中，年龄和缺血的临床相关组合呈现出独特的表型。
