Department of Pharmacology, Israel Institute for Biological Research, Ness Ziona, Israel.
Wound Repair Regen. 2012 Nov-Dec;20(6):852-61. doi: 10.1111/j.1524-475X.2012.00830.x. Epub 2012 Oct 19.
Sulfur mustard induces severe acute and prolonged damage to the skin and only partially effective treatments are available. We have previously validated the use of hairless guinea pigs as an experimental model for skin lesions. The present study aimed to characterize a model of a deep dermal lesion and to compare it with the previously described superficial lesion. Clinical evaluation of the lesions was conducted using reflectance colorimetry, trans-epidermal water loss and wound area measurements. Prostaglandin E(2) content, matrix metalloproteinase-2 and 9 activity, and histopathology were conducted up to 4 weeks post-exposure. Sulfur mustard skin injury, including erythema and edema, impairment of skin barrier and wounds developed in a dose-dependent manner. Prostaglandin E(2) content and matrix metalloproteinase-2 and 9 activities were elevated during the wound development and the healing process. Histological evaluation revealed severe damage to the epidermis and deep dermis and vesications. At 4 weeks postexposure, healing was not completed: significantly impaired stratum corneum, absence of hair follicles, and epidermal hyperplasia were observed. These results confirm the use of the superficial and deep dermal skin injuries in the hairless guinea pigs as suitable models that can be utilized for the investigation of the pathological processes of acute as well as long-term injuries. These models will be further used to develop treatments to improve the healing process and prevent skin damage and long-term effects.
芥子气会对皮肤造成严重的急性和长期损伤,目前仅有部分有效治疗方法。我们之前已经验证了无毛豚鼠作为皮肤损伤实验模型的有效性。本研究旨在对真皮深层损伤模型进行特征描述,并将其与之前描述的真皮浅层损伤模型进行比较。采用反射比色法、经表皮水分丧失和创面面积测量对病变进行临床评估。在暴露后 4 周内进行前列腺素 E2 含量、基质金属蛋白酶-2 和 9 活性及组织病理学检查。芥子气皮肤损伤包括红斑和水肿、皮肤屏障损伤和创面形成均呈现出剂量依赖性。在创面形成和愈合过程中,前列腺素 E2 含量和基质金属蛋白酶-2 和 9 活性升高。组织学评估显示表皮和真皮深层严重损伤和水疱。在暴露后 4 周时,愈合尚未完成:观察到显著受损的角质层、缺失的毛囊和表皮过度增生。这些结果证实了无毛豚鼠的真皮浅层和深层损伤可作为合适的模型,可用于研究急性和长期损伤的病理过程。这些模型将进一步用于开发治疗方法,以改善愈合过程并预防皮肤损伤和长期影响。