Selective inhibition of COX-2 improves cutaneous wound healing of pressure ulcers in mice through reduction of iNOS expression

被引:54
作者
Romana-Souza, Bruna [1 ]
dos Santos, Jeanine Salles [2 ]
Bandeira, Luana Graziella [1 ]
Monte-Alto-Costa, Andrea [1 ]
机构
[1] Univ Estado Rio De Janeiro, Dept Histol & Embryol, Rio De Janeiro, Brazil
[2] Univ Estado Rio De Janeiro, Histocompatibil & Cryopreservat Lab, Rio De Janeiro, Brazil
关键词
Cyclooxygenase-2; Pressure ulcer; Mice; Celecoxib; Prostaglandin E-2; ISCHEMIA-REPERFUSION INJURY; CHRONIC VENOUS ULCERS; NORMAL HUMAN SKIN; OXIDATIVE STRESS; NITRIC-OXIDE; HUMAN KERATINOCYTES; LEG ULCERS; MODEL; CELECOXIB; RATS;
D O I
10.1016/j.lfs.2016.04.017
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Aims: Cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) are involved in chronic inflammation observed in chronic lesions. Nonetheless, neither study demonstrated if decreased COX-2 activation could promote the wound healing of pressure ulcers. Therefore, this study investigated the effect of the administration of celecoxib (a selective COX-2 inhibitor) in wound healing of pressure ulcers. Materials and methods: Male mice were treated daily with celecoxib until euthanasia. One day after the beginning of treatment, two cycles of ischemia-reperfusion by external application of two magnetic plates were performed in skin to induce pressure ulcer formation. Key findings: Celecoxib administration reduced the protein expression of inducible nitric oxide synthase (iNOS), COX-2 and PGE2. The hydroperoxide levels, neutrophil and macrophage number, and protein elastase and matrix metalloproteinase-1 levels were reduced in celecoxib-treated group when compared to control group. Celecoxib administration increased myofibroblastic differentiation, re-epithelialization and wound contraction, and decreased the skin necrosis and angiogenesis. Celecoxib administration also stimulated the formation of a more organized and mature scar increasing collagen deposition and reducing tenascin-C expression. Significance: Celecoxib administration improves the wound healing of pressure ulcers through decreased expression of iNOS and COX-2, which reduces wound inflammation and promotes dermal reconstruction and scar formation. (C) 2016 Elsevier Inc. All rights reserved.
引用
收藏
页码:82 / 92
页数:11
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