Impact of aging on gene expression in a rat model of ischemic cutaneous wound healing.
Impact of aging on gene expression in a rat model of ischemic cutaneous wound healing.
复制标题
衰老对缺血性皮肤伤口愈合大鼠模型基因表达的影响。
DOI：
10.1016/s0022-4804(03)00349-4
复制
发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Mustoe,ThomasA
中科院分区：
文献类型：
--
作者：
Mogford,JonE;Sisco,Mark;Bonomo,SteveR;Robinson,AlanM;Mustoe,ThomasA
背景组织缺血和衰老是与皮肤伤口愈合损伤相关的独立特征。然而，人们对这些与愈合受损的伤口相关的过程的病理生理学知之甚少。材料和方法在年轻（3-6个月）和老年（>24个月）Fisher大鼠的双耳上制作单个全层活检伤口。通过横断耳基部的脉管系统使一只耳朵缺血，而另一只耳朵作为内部非缺血对照。 3至7天收获伤口，并对其肉芽组织形成和上皮化进行组织学评估。使用基于尼龙的 cDNA 阵列探测术后第 7 天收获的伤口总 RNA，以评估整体基因表达变化。 结果通过肉芽组织形成和伤口上皮化测量，缺血和高龄会损害大鼠耳模型的愈合。与年龄相比，肉芽组织形成在更大程度上受到缺血的影响（分别为-58%与-21%），而上皮化则表现出相反的反应（分别为-17%与-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表现出表达改变的基因显着增加。重要的是，在老年缺血性伤口的样本中发现了所有可能的基因表达变化，这表明基因调控不仅仅因高龄而受到抑制。结论高龄对伤口上皮化的影响似乎比缺血更大。结果证明了皮肤伤口愈合体内模型中年龄和缺血的临床相关组合所呈现的独特表型。
BACKGROUNDTissue 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.MATERIALS AND METHODSA 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.RESULTSHealing 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.CONCLUSIONSWound 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.