Department of Emergency Medicine, University of Nebraska Medical Center, Omaha, NE.
Department of Emergency Medicine, University of Nebraska Medical Center, Omaha, NE.
Wilderness Environ Med. 2020 Dec;31(4):407-417. doi: 10.1016/j.wem.2020.07.003. Epub 2020 Oct 16.
Frostbite is thought to result from initial vasoconstriction, ischemia, intracellular ice crystal formation, and inflammation caused by reperfusion injury. Corticosteroids have demonstrated beneficial anti-inflammatory effects in the treatment of other ischemia/reperfusion clinical conditions. The objective of this study was to determine the effect of dexamethasone (dex) on wound healing, inflammatory response, and vasculogenesis in a mouse skin frostbite model.
Treatment and control groups of C57/BL6 mice were subjected to frostbite using a previously described model. Treatment with intraperitoneal dex (1 mg·kg·d) began on the day of frostbite induction and lasted for 7 d. Over 4 wk, we compared wound diameter; morphology by visual inspection, hematoxylin-eosin staining, and Masson's trichrome staining; density of inflammatory cytokines IL-1β and TNFα using Western blot analysis; and formation of microvasculature using immunofluorescence staining. Data were analyzed using 1-way or 1-way repeated-measures analysis of variance.
After frostbite injury, morphological images demonstrated epidermal necrosis and loss in the frostbitten skin as well as infiltration of inflammation-related leukocytes. Increased production of inflammatory cytokines and disappearance of the microvasculature also occurred in the frostbitten skin. In comparison to the control group, treatment with dex promoted wound healing as demonstrated by decreased wound diameter; decreased levels of inflammatory cytokines, and accelerated formation of mature microvasculature.
In this animal model, dex improved wound healing in frostbitten skin and demonstrated both anti-inflammatory effects and stimulation of vasculogenesis. This study suggests that the use of potent anti-inflammatory agents may be an effective strategy for mitigating frostbite injury.
冻伤被认为是由于初始血管收缩、缺血、细胞内冰晶形成以及再灌注损伤引起的炎症反应导致的。皮质类固醇在治疗其他缺血/再灌注临床病症中表现出有益的抗炎作用。本研究的目的是确定地塞米松（dex）在小鼠皮肤冻伤模型中对伤口愈合、炎症反应和血管生成的影响。
使用先前描述的模型对 C57/BL6 小鼠的治疗组和对照组进行冻伤。从冻伤诱导的那一天开始，通过腹腔内给予 dex（1mg·kg·d），并持续 7 天。在 4 周的时间内，我们比较了伤口直径；通过肉眼观察、苏木精-伊红染色和 Masson 三色染色的形态；使用 Western blot 分析炎症细胞因子 IL-1β 和 TNFα 的密度；以及使用免疫荧光染色形成的微血管。使用单向或单向重复测量方差分析来分析数据。
冻伤损伤后，形态学图像显示冻伤皮肤的表皮坏死和丧失，以及炎症相关白细胞的浸润。在冻伤皮肤中也观察到炎症细胞因子的产生增加和微血管的消失。与对照组相比，地塞米松治疗促进了伤口愈合，表现为伤口直径减小；炎症细胞因子水平降低，以及成熟微血管的形成加速。
在这个动物模型中，地塞米松改善了冻伤皮肤的伤口愈合，表现出抗炎作用和刺激血管生成的作用。本研究表明，使用强效抗炎剂可能是减轻冻伤损伤的有效策略。
