Laboratoire Croissance Cellulaire, Réparation, et Régénération Tissulaires, Équipe d'Accueil Conventionnée, Centre National de la Recherche Scientifique 7149, Université Paris-Est Créteil, Créteil, France.
J Pharmacol Exp Ther. 2012 Oct;343(1):115-24. doi: 10.1124/jpet.111.188599. Epub 2012 Jul 5.
Skin wound healing is a natural and intricate process that takes place after injury, involving different sequential phases such as hemostasis, inflammatory phase, proliferative phase, and remodeling that are associated with complex biochemical events. The interruption or failure of wound healing leads to chronic nonhealing wounds or fibrosis-associated diseases constituting a major health problem where, unfortunately, medicines are not very effective. The objective of this study was to evaluate the capacity of Cicaderma ointment (Boiron, Lyon, France) to accelerate ulcer closure without fibrosis and investigate wound healing dynamic processes. We used a necrotic ulcer model in mice induced by intradermal doxorubicin injection, and after 11 days, when the ulcer area was maximal, we applied Vaseline petroleum jelly or Cicaderma every 2 days. Topical application of Cicaderma allowed a rapid recovery of mature epidermal structure, a more compact and organized dermis and collagen bundles compared with the Vaseline group. Furthermore, the expression of numerous cytokines/molecules in the ulcer was increased 11 days after doxorubicin injection compared with healthy skin. Cicaderma rapidly reduced the level of proinflammatory cytokines, mainly tumor necrosis factor (TNF)-α and others of the TNF pathway, which can be correlated to a decrease of polymorphonuclear recruitment. It is noteworthy that the modulation of inflammation through TNF-α, macrophage inflammatory protein-1α, interleukin (IL)-12, IL-4, and macrophage-colony-stimulating factor was maintained 9 days after the first ointment application, facilitating the wound closure without affecting angiogenesis. These cytokines seem to be potential targets for therapeutic approaches in chronic wounds. Our results confirm the use of Cicaderma for accelerating skin wound healing and open new avenues for sequential treatments to improve healing.
皮肤创伤愈合是一种自然而复杂的过程，发生在受伤后，涉及不同的连续阶段，如止血、炎症期、增殖期和重塑期，这些阶段与复杂的生化事件有关。创伤愈合的中断或失败会导致慢性不愈合的伤口或纤维化相关疾病，这构成了一个主要的健康问题，不幸的是，药物对此并不十分有效。本研究的目的是评估 Cicaderma 软膏（Boiron，Lyon，法国）加速无纤维化溃疡愈合的能力，并研究创伤愈合的动态过程。我们使用了一种由真皮内阿霉素注射诱导的坏死性溃疡模型，在第 11 天，当溃疡面积最大时，我们每两天应用凡士林石油凝胶或 Cicaderma。与凡士林组相比，Cicaderma 的局部应用可迅速恢复成熟的表皮结构，真皮更紧凑和有组织，胶原束更规则。此外，与健康皮肤相比，阿霉素注射后 11 天，溃疡中许多细胞因子/分子的表达增加。Cicaderma 迅速降低了促炎细胞因子的水平，主要是肿瘤坏死因子 (TNF)-α 和 TNF 通路的其他细胞因子，这与中性粒细胞募集的减少有关。值得注意的是，通过 TNF-α、巨噬细胞炎症蛋白-1α、白细胞介素 (IL)-12、IL-4 和巨噬细胞集落刺激因子调节炎症，在第一次涂抹软膏后 9 天内得以维持，促进伤口闭合而不影响血管生成。这些细胞因子似乎是慢性伤口治疗方法的潜在靶点。我们的结果证实了 Cicaderma 用于加速皮肤创伤愈合的用途，并为改善愈合的序贯治疗开辟了新的途径。
