糖尿病溃疡中Wnt/β-catenin信号通路表达的变化

目的:观察糖尿病(DM)溃疡中Wnt/β-catenin信号通路表达的变化,探讨该信号通路在糖尿病难愈性溃疡中的作用。方法:雌性Wistar大鼠采用高脂高糖饲料联合小剂量链脲佐菌素液腹腔注射法制备糖尿病模型。分别取正常对照组与DM组制作溃疡模型。观察创面造模后第3天、第7天和第14天对照组及DM组创面愈合情况的变化,并采用HE染色法检测创面组织形态结构的变化,采用ELISA法和RT-PCR法检测创面组织中β-catenin、GSK-3β和Rspo-3蛋白及mRNA的变化。结果:DM组大鼠的创面愈合率明显低于对照组(P0.05),且与对照组相比,其创面组织中含有较少的炎性细胞、纤维母细胞及新生毛细血管。DM组大鼠创面组织中β-catenin和Rspo-3蛋白及mRNA的表达水平均低于对照组,GSK-3β蛋白及mRNA的表达水平均高于对照组(P0.05)。结论:Wnt/β-catenin通路的下调有可能导致了糖尿病溃疡的难愈,而该通路的下调可能源自于Rspo-3蛋白表达的下降。

Expression changes of Wnt/β-catenin signaling pathway in diabetic ulcer

AIM: To observe the effect of Wnt/β-catenin signaling pathway on diabetic ulcer. METHODS: Diabetic animal model was established in the female Wistar rats by intraperitoneal injection of low-dose streptozotocin following high-fat diet feeding. A circular wound was made on the dorsum of the rats in both control group and diabetic group. The condition of wound healing was recorded and the structures of the wound tissues were observed by HE staining in the 2 groups at 3, 7 and 14 d after wounding. The expression of β-catenin, GSK-3β and Rspo-3 at mRNA and protein levels in the wound tissues was detected by RT-PCR and ELISA. RESULTS: In diabetic group, the wound healing rate was lower (P<0.05), and the inflammatory cells, fibroblast cells and new capillaries in the wound tissues were fewer than those in control group. The expression of β-catenin and Rspo-3 at mRNA and protein levels in the wound tissues in control group was significantly higher than those in diabetic group, and the expression of GSK-3β was exactly the opposite (P<0.05). CONCLUSION: The down-regulation of Wnt/β-catenin probably resultes from the decreased level of Rspo-3, which may be one of the reasons for delaying the diabetic ulcer healing.