1.Institute of Dermatology & Hospital for Skin Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College;2.Nanjing Medical University
目的 探究角蛋白17（keratin 17，Krt17）基因敲除对糖尿病小鼠的创面愈合的影响。 方法 取6周龄野生型小鼠和Krt17基因敲除小鼠，利用60%高脂饲料喂养4周和腹腔注射链脲佐菌素（40mg/（kg?d），连续5d）联合诱导建立糖尿病小鼠模型；于造模成功后1周，小鼠异氟烷全身麻醉，背部剃毛，用6 mm环钻制造在体的皮肤圆形损伤；于制造创面后第8天，利用Western blotting和免疫荧光染色检测KRT17在创面近端中的表达和定位及病理组织学分析；并于制造创面后第0、2、4、6和8天拍照记录，计算伤口愈合速率。 结果 在正常生理情况下，KRT17主要在小鼠毛囊中表达；当皮肤受到损伤时，创面近端的角质形成细胞中KRT17的表达显著升高；而糖尿病小鼠创面中KRT17的表达较对照组小鼠显著下调。与野生型小鼠相比，Krt17基因敲除小鼠的伤口愈合速率显著降低；创面局部炎症反应更持续。 结论 Krt17基因敲除加剧了糖尿病小鼠的创面愈合障碍，Krt17可能是参与该病理进程的重要调控基因之一。
Objective To explore the effects of keratin 17 (Krt17) knockout on wound healing in diabetic mice. Methods To establish the diabetic models, 60% high-fat diet was fed and streptozotocin was administered intraperitoneally at 40mg/kg once per day for 5 consecutive days in wild-type (WT) and Krt17 knockout (Krt17-/-) mice at six weeks of age. The mice were anesthetized with isoflurane, the back was shaved, and a 6 mm circular skin lesion was made in vivo at one week after successful modeling. Western blotting and immunofluorescence staining were used to detect the expression and localization of KRT17 and histopathological examination was analyzed in wound healing on the 8th day. Photos were taken at 0, 2, 4, 6 and 8 days after wound manufacturing, and wound healing rate was calculated. Results KRT17 was mainly expressed in mouse hair follicles in physiological conditions. When the skin was injured, the expression of KRT17 in keratinocytes in the proximal wound was significantly increased. However, the expression of KRT17 in wounds of diabetic mice was significantly down-regulated compared with that of control mice. The wound healing rate of Krt17-/- mice was significantly reduced and the local inflammatory reaction was more persistent compared with WT mice. Conclusions Krt17 knockout aggravates wound healing in diabetic mice. Krt17 may be an important modifier gene of diabetic wound healing.