目的 :研究糖尿病 (DM)大鼠皮肤的组织化学改变 ,探讨DM难愈创面形成和发展的病理机制。方法 :用链脲佐菌素 (STZ)将SD大鼠诱导成速发型DM大鼠模型 ,并以正常大鼠作对照 ,分别于致病后 4、8和 12周获取大鼠背部中央的皮肤标本。应用HE染色 ,观察皮肤组织学的改变 ;应用Beckman’s生化自动分析仪检测皮肤组织匀浆的糖含量 ;采用F - 30 10荧光分光光度计测定皮肤胶原提取液的荧光强度 ;应用免疫组化和图像分析技术检测皮肤组织晚期糖基化终末产物 (AGEs)含量。结果 :组织学观察可见 ,DM大鼠表皮组织变薄 ,表皮细胞层次欠清晰 ,部分表皮缺乏复层排列 ;真皮层部分胶原萎缩、肿胀 ,退化变性 ,并伴有程度不等的炎性细胞浸润 ;皮下脂肪进行性萎缩或消失。皮肤糖含量在各时相点均显著高于正常对照 (P <0 . 0 1)。皮肤胶原提取液的荧光值亦高于相应年龄正常鼠 (P <0 0 5 ) ,并随病程增加。AGEs蛋白主要沉积于真皮基质和细胞中 ,以及皮肤血管基底膜周围 ,并随病程的发展 ,染色逐渐加深 ,呈片状。结论 :DM皮肤在损伤前就已发生明显的组织化学改变 ,而这些改变可能是由于局部高糖和AGEs累积所引发 ,并可能是DM难愈创面形成和发展的病理基础之一。 Objective: To study the histochemical changes in the skin of diabetic rats and to explore the pathological mechanism of the formation and development of refractory wounds in DM. Methods: Sprague-Dawley rats were induced by streptozotocin (STZ) and the normal rats were used as the control. The rats were respectively sacrificed at 4, 8 and 12 weeks after the onset of disease specimen. The histological changes of the skin were observed by HE staining. The content of glucose in the skin homogenate was detected by Beckman’s automatic biochemical analyzer. The fluorescence intensity of the skin collagen extract was measured by F - 30 10 fluorescence spectrophotometer. Analytical techniques to detect advanced glycation end products (AGEs) in skin tissue. Results: Histological observation revealed that the epidermis of DM rats became thinner and the epidermis was less clear. Some epidermis lacked the arrangement of stratification. Collagen of the dermis was atrophied, swollen, degenerated and accompanied by varying degrees of inflammatory cell infiltration Subcutaneous fat atrophy or disappear. The content of sugar in the skin at each time point was significantly higher than the normal control (P <0.01). The fluorescence of skin collagen extract also higher than the corresponding age-normal mice (P <0 05), and increased with the course. AGEs proteins were mainly deposited in dermal matrix and cells, as well as around the basement membrane of skin vessels. With the development of the disease course, the staining of AGEs gradually deepened and became flaky. CONCLUSION: The histological changes of DM skin have occurred before injury, and these changes may be caused by the accumulation of local high glucose and AGEs and may be one of the pathological bases for the formation and development of DM refractory wounds.