Sakai Shingo, Endo Yoko, Ozawa Naoko, Sugawara Tomoko, Kusaka Ayumi, Sayo Tetsuya, Tagami Hachiro, Inoue Shintaro
Basic Research Laboratory, Kanebo Ltd, Kanagawa 250-0002, Japan.
J Invest Dermatol. 2003 Jan;120(1):79-85. doi: 10.1046/j.1523-1747.2003.12006.x.
Diabetes mellitus induces many pathophysiologic changes in the skin. Even so, dermatologists still lack an animal model of diabetes that enables the direct evaluation of the various functional properties of the skin. Our group induced two types of an experimental type 1 diabetes model in hairless mice by administering either streptozotocin or alloxan, in order to examine the properties of the stratum corneum and epidermis of these animals. The plasma glucose concentrations of the mice at 3 wk after their i.v. injection were significantly higher than those of control mice (streptozotocin, 3.2-fold; alloxan, 3.7-fold). The stratum corneum water content was significantly reduced in both types of diabetic mice, whereas the transepidermal water loss remained unchanged. The amino acid content with normal epidermal profilaggrin processing was either normal or elevated in the stratum corneum of the streptozotocin-treated mice. In contrast, the stratum corneum triglyceride content in the streptozotocin-treated mice was significantly lower than the control level, even though the levels of ceramides, cholesterols, and fatty acids in the stratum corneum were all higher than the control levels. The streptozotocin-treated group also exhibited decreases in basal cell proliferation and epidermal DNA content linked with an increase in the number of corneocyte layers in the stratum corneum, suggesting that the rates of epidermal and stratum corneum turnover were slower in the streptozotocin-treated animals than in the normal controls. In contrast, there were no remarkable changes in any of the epidermal differentiation marker proteins examined. This finding in diabetic mice, namely, reduction in both the epidermal proliferation and stratum corneum water content without any accompanying impairment in the stratum corneum barrier function, is similar to that found in aged human skin. Our new animal model of diabetes will be useful for the study of diabetic dermopathy as well as the mechanisms of stratum corneum moisturization.
糖尿病会在皮肤中引发多种病理生理变化。即便如此,皮肤科医生仍缺乏一种能够直接评估皮肤各种功能特性的糖尿病动物模型。我们的研究小组通过给无毛小鼠注射链脲佐菌素或四氧嘧啶,诱导出了两种实验性1型糖尿病模型,以研究这些动物角质层和表皮的特性。静脉注射后3周,小鼠的血浆葡萄糖浓度显著高于对照小鼠(链脲佐菌素组为3.2倍;四氧嘧啶组为3.7倍)。两种糖尿病小鼠的角质层含水量均显著降低,而经表皮水分流失保持不变。链脲佐菌素处理的小鼠角质层中,具有正常表皮聚丝蛋白加工过程的氨基酸含量正常或升高。相比之下,链脲佐菌素处理的小鼠角质层甘油三酯含量显著低于对照水平,尽管角质层中神经酰胺、胆固醇和脂肪酸的水平均高于对照水平。链脲佐菌素处理组还表现出基底细胞增殖和表皮DNA含量下降,同时角质层中角质形成细胞层数增加,这表明链脲佐菌素处理的动物表皮和角质层的更新速率比正常对照组慢。相比之下,所检测的任何表皮分化标志物蛋白均无明显变化。糖尿病小鼠的这一发现,即表皮增殖和角质层含水量均降低,而角质层屏障功能未伴随任何损害,与老年人皮肤的情况相似。我们新的糖尿病动物模型将有助于研究糖尿病性皮肤病以及角质层保湿机制。