Davis Thomas A, Stojadinovic Alexander, Anam Khairul, Amare Mihret, Naik Shruti, Peoples George E, Tadaki Douglas, Elster Eric A
Combat Casualty Care, Department of Regenerative Medicine, Naval Medical Research Center, Silver Spring, MD 20910, USA.
Int Wound J. 2009 Feb;6(1):11-21. doi: 10.1111/j.1742-481X.2008.00540.x.
Following severe burn injury, persistent inflammation perpetuated by surface eschar, bacterial colonisation and neutrophil proteolytic activity can impede normal healing and result in further tissue damage. Extracorporeal shock wave treatment (ESWT) has been shown in the clinical setting to promote the healing of burn and difficult-to-heal wounds; however, the mechanism is unclear. We investigated the role of ESWT on the early proinflammatory response using a severe, full-thickness and highly inflammatory cutaneous burn wound in a murine model. Various wound-healing parameters were measured and leukocyte infiltration quantitated. A panel of 188 candidate genes known to be involved in acute inflammation and wound healing was screened. We show that ESWT of burn wounds 1 hour postwounding significantly blunts polymorphonuclear neutrophil and macrophage infiltration into the wound. ESWT treatment potently attenuates both CC- and CXC-chemokine expression, acute proinflammatory cytokine expression and extracellular matrix proteolytic activity at the wound margin. Given these findings and the clinical success of ESWT, we speculate that ESWT may be a potential therapeutic modality to treat severe wounds wherein excessive inflammatory responses involving increased levels of inflammatory cells, proinflammatory cytokines and proteases may become self-resolving allowing wound healing to progresses by way of normal physiological repair processes.
严重烧伤后,由表面焦痂、细菌定植和中性粒细胞蛋白水解活性持续引发的炎症会阻碍正常愈合,并导致进一步的组织损伤。在临床环境中,体外冲击波治疗(ESWT)已被证明可促进烧伤和难愈合伤口的愈合;然而,其机制尚不清楚。我们使用小鼠模型中的严重、全层且高度炎症性的皮肤烧伤伤口,研究了ESWT对早期促炎反应的作用。测量了各种伤口愈合参数,并对白细胞浸润进行了定量。筛选了一组已知参与急性炎症和伤口愈合的188个候选基因。我们发现,伤后1小时对烧伤伤口进行ESWT可显著减少多形核中性粒细胞和巨噬细胞向伤口的浸润。ESWT治疗可有效减弱伤口边缘的CC趋化因子和CXC趋化因子表达、急性促炎细胞因子表达以及细胞外基质蛋白水解活性。鉴于这些发现以及ESWT在临床上的成功应用,我们推测ESWT可能是一种治疗严重伤口的潜在治疗方式,在严重伤口中,涉及炎症细胞、促炎细胞因子和蛋白酶水平升高的过度炎症反应可能会自行消退,从而使伤口通过正常的生理修复过程得以愈合。