Ud-Din Sara, Sebastian Anil, Giddings Pamela, Colthurst James, Whiteside Sigrid, Morris Julie, Nuccitelli Richard, Pullar Christine, Baguneid Mo, Bayat Ardeshir
Plastic & Reconstructive Surgery Research, Manchester Institute of Biotechnology, University of Manchester, Manchester, United Kingdom; University Hospital of South Manchester NHS Foundation Trust, Institute of Inflammation and Repair, Faculty of Medical and Human Sciences, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom.
Plastic & Reconstructive Surgery Research, Manchester Institute of Biotechnology, University of Manchester, Manchester, United Kingdom.
PLoS One. 2015 Apr 30;10(4):e0124502. doi: 10.1371/journal.pone.0124502. eCollection 2015.
Angiogenesis is critical for wound healing. Insufficient angiogenesis can result in impaired wound healing and chronic wound formation. Electrical stimulation (ES) has been shown to enhance angiogenesis. We previously showed that ES enhanced angiogenesis in acute wounds at one time point (day 14). The aim of this study was to further evaluate the role of ES in affecting angiogenesis during the acute phase of cutaneous wound healing over multiple time points. We compared the angiogenic response to wounding in 40 healthy volunteers (divided into two groups and randomised), treated with ES (post-ES) and compared them to secondary intention wound healing (control). Biopsy time points monitored were days 0, 3, 7, 10, 14. Objective non-invasive measures and H&E analysis were performed in addition to immunohistochemistry (IHC) and Western blotting (WB). Wound volume was significantly reduced on D7, 10 and 14 post-ES (p = 0.003, p = 0.002, p<0.001 respectively), surface area was reduced on days 10 (p = 0.001) and 14 (p<0.001) and wound diameter reduced on days 10 (p = 0.009) and 14 (p = 0.002). Blood flow increased significantly post-ES on D10 (p = 0.002) and 14 (p = 0.001). Angiogenic markers were up-regulated following ES application; protein analysis by IHC showed an increase (p<0.05) in VEGF-A expression by ES treatment on days 7, 10 and 14 (39%, 27% and 35% respectively) and PLGF expression on days 3 and 7 (40% on both days), compared to normal healing. Similarly, WB demonstrated an increase (p<0.05) in PLGF on days 7 and 14 (51% and 35% respectively). WB studies showed a significant increase of 30% (p>0.05) on day 14 in VEGF-A expression post-ES compared to controls. Furthermore, organisation of granulation tissue was improved on day 14 post-ES. This randomised controlled trial has shown that ES enhanced wound healing by reduced wound dimensions and increased VEGF-A and PLGF expression in acute cutaneous wounds, which further substantiates the role of ES in up-regulating angiogenesis as observed over multiple time points. This therapeutic approach may have potential application for clinical management of delayed and chronic wounds.
血管生成对伤口愈合至关重要。血管生成不足会导致伤口愈合受损和慢性伤口形成。电刺激（ES）已被证明可促进血管生成。我们之前的研究表明，ES在一个时间点（第14天）可促进急性伤口的血管生成。本研究的目的是进一步评估ES在皮肤伤口愈合急性期多个时间点对血管生成的影响。我们比较了40名健康志愿者（分为两组并随机分组）在接受ES治疗（ES后）后伤口的血管生成反应，并将其与二期愈合伤口（对照组）进行比较。监测的活检时间点为第0、3、7、10、14天。除免疫组织化学（IHC）和蛋白质印迹法（WB）外，还进行了客观的非侵入性测量和苏木精-伊红（H&E）分析。ES后第7、10和14天伤口体积显著减小（分别为p = 0.003、p = 0.002、p<0.001），第10天（p = 0.001）和第14天（p<0.001）伤口表面积减小，第10天（p = 0.009）和第14天（p = 0.002）伤口直径减小。ES后第10天（p = 0.002）和第14天（p = 0.001）血流量显著增加。应用ES后血管生成标志物上调；IHC蛋白质分析显示，与正常愈合相比，ES治疗在第7、10和14天VEGF-A表达增加（分别为39%、27%和35%），在第3天和第7天PLGF表达增加（两天均为40%）。同样，WB显示第7天和第14天PLGF增加（分别为51%和35%）。WB研究显示，与对照组相比，ES后第14天VEGF-A表达显著增加30%（p>0.05）。此外，ES后第14天肉芽组织的结构得到改善。这项随机对照试验表明，ES通过减小急性皮肤伤口的尺寸以及增加VEGF-A和PLGF表达来促进伤口愈合，这进一步证实了ES在多个时间点上调血管生成中的作用。这种治疗方法可能在延迟性和慢性伤口的临床管理中有潜在应用价值。
