Roy Sashwati, Biswas Sabyasachi, Khanna Savita, Gordillo Gayle, Bergdall Valerie, Green Jeanne, Marsh Clay B, Gould Lisa J, Sen Chandan K
Comprehensive Wound Center, Davis Heart and Lung Research Institute, Department of Surgery, The Ohio State University Medical Center, Columbus, Ohio 43210, USA.
Physiol Genomics. 2009 May 13;37(3):211-24. doi: 10.1152/physiolgenomics.90362.2008. Epub 2009 Mar 17.
Chronic ischemic wounds presenting at wound clinics are heterogeneous with respect to etiology, age of the wound, and other factors complicating wound healing. In addition, there are ethical challenges associated with collecting repeated biopsies from a patient to develop an understanding of the temporal dynamics of the mechanisms underlying chronic wounds. The need for a preclinical model of ischemic wound is therefore compelling. The porcine model is widely accepted as an excellent preclinical model for human wounds. A full-thickness bipedicle flap approach was adopted to cause skin ischemia. Closure of excisional wounds placed on ischemic tissue was severely impaired resulting in chronic wounds. Histologically, ischemic wounds suffered from impaired re-epithelialization, delayed macrophage recruitment and poorer endothelial cell abundance and organization. Compared with the pair-matched nonischemic wound, unique aspects of the ischemic wound biology were examined on days 3, 7, 14, and 28 by systematic screening of the wound tissue transcriptome using high-density porcine GeneChips. Ischemia markedly potentiated the expression of arginase-1, a cytosolic enzyme that metabolizes the precursor of nitric oxide l-arginine. Ischemia also induced the SOD2 in the wound tissue perhaps as survival response of the challenged tissue. Human chronic wounds also demonstrated elevated expression of SOD2 and arginase-1. This study provides a thorough database that may serve as a valuable reference tool to develop novel hypotheses aiming to elucidate the biology of ischemic chronic wounds in a preclinical setting.
在伤口诊所出现的慢性缺血性伤口在病因、伤口形成时间以及其他影响伤口愈合的因素方面存在异质性。此外，从患者身上采集重复活检样本以了解慢性伤口潜在机制的时间动态变化存在伦理挑战。因此，迫切需要一种缺血性伤口的临床前模型。猪模型被广泛认为是一种优秀的人类伤口临床前模型。采用全厚双蒂皮瓣法造成皮肤缺血。放置在缺血组织上的切除伤口的闭合严重受损，导致慢性伤口形成。组织学上，缺血性伤口存在上皮再形成受损、巨噬细胞募集延迟以及内皮细胞数量和排列较差的情况。与配对的非缺血性伤口相比，在第3、7、14和28天通过使用高密度猪基因芯片系统筛选伤口组织转录组，研究了缺血性伤口生物学的独特方面。缺血显著增强了精氨酸酶-1的表达，精氨酸酶-1是一种代谢一氧化氮前体L-精氨酸的胞质酶。缺血还诱导伤口组织中的超氧化物歧化酶2（SOD2）表达，这可能是受挑战组织的一种存活反应。人类慢性伤口也表现出SOD2和精氨酸酶-1的表达升高。本研究提供了一个全面的数据库，可作为一个有价值的参考工具，用于提出新的假设，旨在阐明临床前环境中缺血性慢性伤口的生物学特性。
