目的：探讨维生素D治疗对糖尿病全层皮肤缺损小鼠促进创面愈合的机制。方法：采用腹腔注射链脲佐菌素(STZ)诱导糖尿病模型,30只小鼠造模成功后分别记录基线资料并按照随机表法分为对照组(NVD组)、低剂量维生素D治疗组I(VDI组)和高剂量维生素D治疗组II(VDII组)各10 只。分别在治疗1、3、7、14 天后以 NIH ImageJ 图像分析软件测量创面面积、计算创面愈合率； 光镜下观察创面肉芽组织生长情况；双抗体夹心酶联免疫吸附法(ELASA)对创面组织中炎症因子(TNF-a、IL-6)行定量分析；聚合酶链反应(PCR)检测创面MMP 9、TIMP1 mRNA水平。结果：总体来看,三组小鼠创面愈合率随时间的延长而增加,其中VDⅡ组在14d时创面愈合率最高(80.86±18.77),差异有统计学意义(P<0.01)。VDⅡ组较VDI组及对照组肉芽组织生长更为明显、表现为较多成纤维细胞和大量新生血管生成、炎性细胞减少。VDII组、VDI组与对照组相比,25(OH)₂VitD、TIMP1 mRNA水平升高, TNF-a、IL-6、 MMP 9mRNA水平下降( P <0.01)；其中VDII组较VDI组25(OH)₂VitD、TIMP1 mRNA升高更明显( P <0.01)且TNF-a、IL-6、MMP 9mRNA水平降低更明显( P <0.01)。结论：维生素D对糖尿病全层皮肤缺损小鼠具有较好的皮肤伤口愈合作用、且呈剂量依赖性；维生素D可以通过抑制创面炎症因子TNF-a、IL-6的表达,降低MMP 9mRNA、提高TIMP1 mRNA水平促进创面愈合。

Objective: To investigate the mechanism of vitamin D treatment in promoting wound healing in diabetic mice with full-thickness skin defect. Methods: Diabetes model was include injectioning of streptozotocin (STZ) in mice abdominal cavity. Thirty mice with successful modeling were recorded with baseline data and divided into control group (NVD group) and low-dose vitamin D treatment group (VDI group) and high-dose vitamin D treatment group (VDII group) with 10 each group according to random table method. NIH ImageJ image analysis software was used to measure the wound area and calculate the wound healing rate after1,3, 7 and 14 days of treatment respectively; the growth of granulation tissue in the wound was observed under light microscope. Double-antibody enzyme-linked immuno assay (ELASA) quantitative analysis of inflammatory factors (TNF-a, IL-6) in wound tissue；polymerase chain reaction (PCR) was used to detect the MMP 9 and TIMP1 of the wound. Results: Overall, the wound healing rates of the three groups of mice increased with time, and the VDⅡ group had the highest wound healing rate at 14 days (80.86±18.77) , the difference was statistically significant (P<0.01). Compared with the VDI group and the control group, the VDⅡ group showed more obvious growth of granulation tissue, more fibroblast formation, a large number of angiogenesis, and decreased inflammatory cells. Compared with the control group, the VDII group and the VDI group increased the levels of 25(OH)2VitD and TIMP1 mRNA ( P < 0.01), while the levels of TNF-a 、IL-6 and MMP9 mRNA are decreased, the difference was statistically significant ( P < 0.01) . Conclusion: Vitamin D has a better skin wound healing effect on diabetic injured mice in a dose-dependent manner; vitamin D can reduce the expression of wound inflammatory factors such as TNF-a 、IL-6 and MMP9 mRNA ;While vitamin D increase TIMP1 mRNA levels . With these method vitamin D can promoting wound healing.

内蒙古自然科学基金