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Comparative Analysis of Angiogenic Gene Expression in Normal and Impaired Wound Healing in Diabetic Mice: Effects of Extracorporeal Shock Wave Therapy

机译:糖尿病小鼠正常和创伤受损愈合过程中血管生成基因表达的比较分析:体外冲击波治疗的效果

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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- alpha). 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.

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