Regenerative Medicine Department, Operational and Undersea Medicine Directorate, Naval Medical Research Center, Room 2W06, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA.
Angiogenesis. 2010 Dec;13(4):293-304. doi: 10.1007/s10456-010-9186-9. Epub 2010 Sep 17.
Impaired wound healing is a persistent clinical problem which has been treated with mixed results. Studies aimed at elucidating the mechanism of impaired wound healing have focused on small cohorts of genes which leave an incomplete picture of the wound healing process. We aimed to investigate impaired wound healing via a comprehensive panel of angiogenic/inflammation-related genes and wound closure kinetics with and without the application of extracorporeal shock wave therapy (ESWT), which has been demonstrated to improve wound healing. Full-thickness skin from the dorsal surface of "normal" (BALB/c) and "impaired" (db (+)/db (+)) mice was excised, and wound margin tissue was harvested 2, 7, and 10 days post injury. A separate, but identical wound model was established over 40 days in order to measure wound closure kinetics. Over time, the normal non-ESWT treated wounds exhibited varying patterns of elevated expression of 25-30 genes, whereas wounds with impaired healing displayed prolonged elevated expression of only a few genes (CXCL2, CXCL5, CSF3, MMP9, TGF-α). In response to ESWT, gene expression was augmented in both types of wounds, especially in the expression of PECAM-1; however, ESWT had no effect on wound closure in either model. In addition, multiple doses of ESWT exacerbated the delayed wound healing, and actually caused the wounds to initially increase in size. These data provide a more complete picture of impaired wound healing, and a way to evaluate various promising treatments.
伤口愈合受损是一个持续存在的临床问题，其治疗效果参差不齐。旨在阐明伤口愈合受损机制的研究集中在少数几个基因上，这些研究对伤口愈合过程的描述并不完整。我们旨在通过研究与血管生成/炎症相关的一组全面基因以及有无体外冲击波治疗（ESWT）的情况下的伤口闭合动力学来研究伤口愈合受损，ESWT 已被证明可以改善伤口愈合。从“正常”（BALB/c）和“受损”（db（+）/db（+））小鼠背部表面切除全层皮肤，并在损伤后 2、7 和 10 天采集伤口边缘组织。为了测量伤口闭合动力学，还建立了一个单独但相同的伤口模型，持续 40 天。随着时间的推移，正常未经 ESWT 治疗的伤口表现出 25-30 个基因的表达升高的不同模式，而愈合受损的伤口仅显示少数基因（CXCL2、CXCL5、CSF3、MMP9、TGF-α）的延长升高表达。对 ESWT 的反应，两种类型的伤口中的基因表达都增强了，特别是 PECAM-1 的表达；然而，ESWT 对两种模型的伤口闭合均无影响。此外，多次 ESWT 加重了延迟的伤口愈合，实际上导致伤口最初增大。这些数据提供了伤口愈合受损的更完整的图景，以及评估各种有前途的治疗方法的方法。
