目的 探讨甜菜碱对糖尿病足大鼠创面愈合及AMPK/SIRT1/FoxO1通路的影响。方法 SD大鼠随机分为对照组、模型组、二甲双胍（200 mg·kg-1，ig给药）组和甜菜碱低、高剂量（50、100 mg ·kg-1，ip给药）组，每组18只。除对照组外，其余组大鼠均构建糖尿病足模型。检测大鼠空腹血糖水平和创面愈合率；ELISA法检测大鼠血清炎性因子白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）、C反应蛋白（CRP）水平；HE染色检测大鼠创面皮肤组织病理学改变；免疫组化染色检测大鼠创面皮肤组织中CD31蛋白阳性表达；试剂盒法检测大鼠创面皮肤组织中氧化应激指标超氧化物歧化酶（SOD）活性、丙二醛（MDA）含量；Western blotting检测大鼠创面皮肤组织中AMP依赖的蛋白激酶（AMPK）/沉默信息调节因子相关酶1（SIRT1）/叉头框蛋白1（FoxO1）通路相关蛋白表达。结果 给药结束后，与对照组比较，模型组大鼠空腹血糖、血清IL-6、TNF-α、CRP水平以及创面皮肤组织中MDA含量和p-FoxO1/FoxO1值显著升高，创面愈合率和创面皮肤组织中CD31阳性表达率、SOD活性、p-AMPK/AMPK值和SIRT1蛋白表达水平显著降低（P<0.05），且创面皮肤组织病理学损伤严重；与模型组比较，甜菜碱低、高剂量组和二甲双胍组大鼠空腹血糖、血清IL-6、TNF-α、CRP水平以及创面皮肤组织中MDA含量和p-FoxO1/FoxO1值显著降低，创面愈合率和创面皮肤组织中CD31阳性表达率、SOD活性、p-AMPK/AMPK值和SIRT1蛋白表达水平显著升高（P<0.05），且创面皮肤组织病理学损伤均有不同程度改善，且甜菜碱高剂量组和二甲双胍组上述指标变化更为明显。结论 甜菜碱可激活AMPK/SIRT1/FoxO1通路，减轻糖尿病足大鼠氧化应激和炎症反应，促进血管生成，加速创面愈合。
Objective To explore the effects of betaine on wound healing and AMPK/SIRT1/FoxO1 pathway in diabetes foot rats. Methods SD rats were randomly grouped into control group, model group, betaine (low and high) dose group (50, 100 mg·kg-1) and metformin group (200 mg ·kg-1), with 18 rats in each group. Except the control group, the rats in the other groups were constructed with diabetes foot models. The fasting blood glucose level and wound healing rate were measured. The levels of serum inflammatory factors (IL-6, TNF-α, CRP) were detected by ELISA. HE staining was applied to detect the histopathological changes of the wound skin. Immunohistochemical staining was applied to detect the positive expression of CD31 protein in the wound skin tissue of rats. The level of oxidative stress index (SOD activity, MDA content) in rat wound skin tissue was detected by commercial kit. Western blotting was applied to detect the expression of AMPK/SIRT1/FoxO1 pathway related protein in rat wound skin tissue.Results After administration, compared with the control group, the fasting blood glucose, serum IL-6, TNF-α, CRP levels, and the MDA content and p-FoxO1/FoxO1 ratio in the wound skin tissue of the model group were higher, the wound healing rate, the positive expression rate of CD31, the activity of SOD, the ratio of p-AMPK/AMPK and the expression level of SIRT1 protein in the wound skin tissue were lower (P< 0.05), the histopathological damage of the wound skin was serious. Compared with the model group, the fasting blood glucose, serum IL-6, TNF-α, CRP levels, and the MDA content and p-FoxO1/FoxO1 ratio in the wound skin tissue of rats in betaine (low and high) dose groups and metformin group were lower, the wound healing rate, the positive expression rate of CD31, the activity of SOD, the ratio of p-AMPK/AMPK and the expression level of SIRT1 protein in the wound skin tissue were higher (P< 0.05), in addition, the histopathological damage of the wound skin was improved to varying degrees, the changes of the above indexes were more obvious in betaine high-dose group and metformin group. Conclusion Betaine can activate AMPK/SIRT1/FoxO1 pathway, alleviate oxidative stress and inflammatory reaction, promote angiogenesis and accelerate wound healing in diabetes foot rats.