糖尿病足溃疡动物模型的建立

Establishment of animal model of diabetic foot ulcer

目的建立一种简单、稳定和重复性好的犬糖尿病足溃疡模型，为干细胞移植的实验研究及临床血管内介入操作提供合适的模型。方技选用毕格犬6只，实验组（n=4）静脉注射四氧嘧啶，对照组（n=2）注射等量生理盐水，两组均行左下肢压迫器植入，同时手术结扎左侧股动脉，3—5d后除去压迫装置。监测两组用药前后空腹血糖（FPG）及餐后2h血糖（PG2h）、体质量和饮食的变化。术后1周和4周行数字减影血管造影（DSA）观察血管情况；4周后处死动物，行溃疡周围组织学检查。结果实验组模型制备成功，用药后FPG和PG2h均明显升高（P〈0．05），体质量下降，饮食明显增加；而对照组FPG、PG2h、体质量和饮食用药前后均无统计学差异（P〉0．05）。术后即刻两组溃疡形态无明显差异；术后4周对照组溃疡基本痊愈，实验组基本不愈合。DSA显示术后1周两组无明显差异；4周时，对照组可见大量新生血管形成，而实验组新生侧枝血管不丰富。组织学检查实验组可见大量坏死组织伴炎细胞浸润。结论该法制备的犬糖尿病足溃疡模型方法简单，成功率高，可以为干细胞移植基础研究以及临床介入血管内操作的研究提供稳定的模型。

Objective To establish a simple, stable and reproducible animal model of diabetic foot ulcer for the research of endovascular therapy and stem cell transplantation. Methods Six canines were randomly divided into control group （n = 2） and experiment group （n = 4）. Canines in experiment group were intravenously injected alloxan while those in control group were injected normal saline instead. All canines were performed compression device implantation and iliac-femoral artery surgical ligation in the left leg. Compression devices were removed after 3 to 5 days. Changes of fasting plasma glucose （FPG） , postprandial 2h blood glucose （PG2h）, body weight and diet before and after medication were monitored in both groups. Digital substraction angiography（DSA） was performed 1 and 4 weeks after operation to observe the vessel changes, and then all canines were sacrificed for histological examination. Results Diabetic models were successfully established in all 4 canines in experiment group, and FPG and PG2h were significantly increased （P 〈0.05） , with a decrease of body weight and increase of diet after medication. While the canines in control group experienced no changes in FPG, PG2h, diet and body weight （P 〉 0.05）. There were no significant differences in morphology of ulcers in both groups right postoperation. Ulcers in control group healed after 4 weeks, while those in experiment group stayed unhealed after 4 weeks. DSA indicated no differences in both groups after 1 week; but demonstrated small amount of new vessels formation in experiment group and a lot of new vessels formation in control group after 4 weeks. Histological examination revealed a large amout of necrosis tissue accompanied by inflammatory cell infiltration. Conclusion This canine model of diabetic foot ulcer is easy to establish and well reproducible, which provides a stable model for the research of clinical intravascular therapy and stem cell transplantation.