Department of Endocrinology, Chang Zheng Hospital, Second Military Medical University, Shanghai, China.
Exp Dermatol. 2010 Dec;19(12):1088-95. doi: 10.1111/j.1600-0625.2010.01137.x.
Pathological and physiological changes in dermal tissue in a rat model of diabetes mellitus (DM) were investigated. Sixteen male 8-week-old Sprague-Dawley rats were randomized into two groups of eight, the DM group (Group DM) and the normal control group (Group (NC) normal control). Group DM rats were injected with streptozotocin (STZ) intraperitoneally at a dose of 65 mg/kg body weight. Group NC rats were injected with the same volume of citric acid buffer. All rats were sacrificed 12 weeks later. The impact of exposure to (AGE) advanced glycation end products-modified human serum albumin (AGE-HSA) on epidermal cells and ECV304 cells was evaluated in cell culture experiments. The diabetic rats exhibited changes in skin tissue, including a decrease in thickness, disappearance of the multilayer epithelium structure, degeneration of collagen fibres and an increase in the infiltration of inflammatory cells, in addition to a significant increase in skin glucose and AGEs. Moreover, diabetic rats had increased plasma glycosylated protein (GSP) and malondialdehyde (MDA) and decreased plasma glutathione (GSH). The percentage of epidermal cells in S phase was similar between the two group rats; however, there was a marked decrease in the G2/M phase in Group DM. Additionally, exposure of ECV304 cells to AGE-HSA led to a time-dependent and dose-dependent increase in apoptosis. Therefore, the high glucose in the skin tissue, coupled with the accumulation of toxic substances such as AGEs, promote the dysfunction of dermal cells and/or the matrix. This may be a significant mechanism of diabetes-induced early-stage endogenous skin damage.
研究了糖尿病（DM）大鼠模型中皮肤组织的病理和生理变化。将 16 只 8 周龄雄性 Sprague-Dawley 大鼠随机分为两组，每组 8 只，即糖尿病组（DM 组）和正常对照组（NC 正常对照组）。DM 组大鼠腹腔注射链脲佐菌素（STZ），剂量为 65mg/kg 体重。NC 组大鼠注射相同体积的柠檬酸缓冲液。所有大鼠均在 12 周后处死。在细胞培养实验中，评估了（AGE）晚期糖基化终产物修饰人血清白蛋白（AGE-HSA）对表皮细胞和 ECV304 细胞的影响。糖尿病大鼠的皮肤组织发生变化，包括厚度减小、多层上皮结构消失、胶原纤维变性和炎症细胞浸润增加，以及皮肤葡萄糖和 AGEs 显著增加。此外，糖尿病大鼠的血浆糖化蛋白（GSP）和丙二醛（MDA）增加，血浆谷胱甘肽（GSH）减少。两组大鼠表皮细胞 S 期的百分比相似；然而，DM 组 G2/M 期明显减少。此外，ECV304 细胞暴露于 AGE-HSA 后，细胞凋亡呈时间依赖性和剂量依赖性增加。因此，皮肤组织中的高血糖，加上 AGE 等有毒物质的积累，促进了真皮细胞和/或基质的功能障碍。这可能是糖尿病引起早期内源性皮肤损伤的重要机制。
