Characterization of a preclinical model of chronic ischemic wound
Characterization of a preclinical model of chronic ischemic wound
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DOI：
10.1152/physiolgenomics.90362.2008
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发表时间：
2009-05-01
影响因子：
4.6
通讯作者：
Sen, Chandan K.
中科院分区：
文献类型：
--
作者：
Roy, Sashwati;Biswas, Sabyasachi;Sen, Chandan K.
Roy S, Biswas S, Khanna S, Gordillo G, Bergdall V, Green J, Marsh CB, Gould LJ, Sen CK。慢性缺血性伤口临床前模型的研究。中国生物医学工程学报（英文版），2009。首次发表于2009年3月17日；doi: 10.1152 / physiolgenomics.90362.2008。在伤口诊所出现的慢性缺血性伤口在病因、伤口年龄和其他影响伤口愈合的因素方面是不同的。此外，从患者身上反复收集活检以了解慢性伤口机制的时间动态也存在伦理挑战。因此，迫切需要临床前缺血性伤口模型。猪模型被广泛认为是一种很好的人体创伤临床前模型。采用全层双蒂皮瓣法引起皮肤缺血。在缺血组织上切除伤口的闭合严重受损，导致慢性伤口。组织学上，缺血性伤口的再上皮化受损，巨噬细胞募集延迟，内皮细胞丰度和组织较差。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，精氨酸酶是一种代谢一氧化氮前体l -精氨酸的细胞质酶。缺血也诱导了创面组织中SOD2的表达，这可能是受损组织的生存反应。人类慢性伤口也表现出SOD2和精氨酸酶-1的表达升高。本研究提供了一个完整的数据库，可以作为一个有价值的参考工具，以发展新的假设，旨在阐明临床前缺血性慢性伤口的生物学。
Roy S, Biswas S, Khanna S, Gordillo G, Bergdall V, Green J, Marsh CB, Gould LJ, Sen CK. Characterization of a preclinical model of chronic ischemic wound. Physiol Genomics 37: 211-224, 2009. First published March 17, 2009; doi:10.1152/physiolgenomics.90362.2008. 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.