【目的】 观察黄芩苷对糖尿病足溃疡（DFU）大鼠新的治疗作用及机制。【方法】 将SD大鼠随机分为对照组，模型组，黄 芩苷低、高剂量组，黄芩苷高剂量+YC-1[缺氧诱导因子 1α（HIF-1α）抑制剂]组。除对照组，其他各组大鼠构建 DFU 模型。 造模成功后，分组给药。给药结束后，检测大鼠空腹血糖水平，计算创面愈合率，酶联免疫吸附分析（ELISA）检测创面肉芽 组织白细胞介素（IL）-10、肿瘤坏死因子（TNF）-α和 IL-6水平，采用羟胺法检测创面肉芽组织超氧化物歧化酶（SOD）活性、 钼酸铵法检测过氧化氢酶（CAT）活性、硫代巴比妥酸法检测丙二醛（MDA）含量，采用苏木精-伊红（HE）染色法观察大鼠创面 肉芽组织形态，免疫组织化学法检测大鼠创面肉芽组织中CD31蛋白阳性表达，Western Blot法检测大鼠创面肉芽组织中晚期 糖基化终末产物（AGEs）、晚期糖基化终末产物受体（RAGE）、基质金属蛋白酶 2（MMP-2）、HIF-1α、血管内皮生长因子 （VEGF）、血管内皮生长因子受体 2（VEGFR-2）蛋白表达。【结果】 与对照组比较，模型组大鼠创面肉芽组织血管生成减少、 炎性细胞浸润明显，空腹血糖水平，创面组织TNF-α、IL-6水平，MDA含量，AGEs、RAGE和MMP-2蛋白表达水平升高， 创面愈合率，创面组织 CD31阳性表达率，IL-10水平，SOD 和 CAT 活性，HIF-1α、VEGF 和 VEGFR-2蛋白表达水平降低， 差异均有统计学意义（P＜0.05）；与模型组比较，黄芩苷低、高剂量组大鼠创面肉芽组织形态明显好转，空腹血糖水平，创面 组织TNF-α、IL-6水平，MDA含量，AGEs、RAGE和MMP-2蛋白表达水平降低，创面愈合率，创面组织CD31阳性表达率， IL-10水平，SOD和CAT活性，HIF-1α、VEGF和VEGFR-2蛋白表达水平升高，差异均有统计学意义（P＜0.05）；YC-1可部 分逆转黄芩苷对DFU大鼠血管生成和炎症的改善作用（P＜0.05）。【结论】 黄芩苷可通过激活HIF-1α/VEGF信号通路减轻DFU 大鼠炎症和氧化应激，促进血管生成和创面愈合。

Objective To observe the new therapeutic effects and mechanisms of baicalin on diabetic foot ulcer （DFU） rats. Methods SD rats were randomly divided into a control group，a model group，a low-dose baicalin group，a high-dose baicalin group，and a high-dose baicalin + YC-1 [hypoxia-inducible factor 1α（HIF-1α） inhibitor] group. Except for the normal group，the rats in all other groups were constructed to DFU model. After successful modeling，the medication was performed in each group. After treatment，fasting blood glucose level was measured，and the wound healing rate was calculated. Enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of interleukin （IL）-10，tumor necrosis factor （TNF）-α，and IL-6 in wound granulation tissue. The hydroxylamine method was used to measure superoxide dismutase （SOD） activity，the ammonium molybdate method was used to measure catalase （CAT） activity， and the thiobarbituric acid method was used to measure malondialdehyde （MDA） content in wound granulation tissue. Hematoxylin-eosin （HE） staining was used to observe the morphology of wound granulation tissue. Immunohistochemistry was used to detect the positive expression of CD31 protein in wound granulation tissue. Western Blot was used to measure the protein expression levels of advanced glycation end products （AGEs）， receptor for advanced glycation end products （RAGE）， matrix metalloproteinase 2（MMP-2）， HIF-1α， vascular endothelial growth factor （VEGF）， and vascular endothelial growth factor receptor 2（VEGFR-2） in wound granulation tissue. Results Compared with the control group， the model group showed reduced angiogenesis and obvious inflanmatory cell infiltration in wound granulation tissue，increased fasting blood glucose level，levels of TNF-α and IL-6，MDA content，and protein expressions of AGEs，RAGE，and MMP-2 in wound tissue，as well as decreased wound healing rate，CD31- positive expression rate， IL-10 level， SOD and CAT activities， and protein expressions of HIF-1α， VEGF， and VEGFR-2，with statistically significant differences（P＜0.05）. Compared with the model group，the low- and high-dose baicalin groups showed significantly improved wound granulation tissue morphology， reduced fasting blood glucose level，levels of TNF-α and IL-6，MDA content，and protein expressions of AGEs，RAGE，and MMP-2 in wound tissue，as well as increased wound healing rate，CD31-positive expression rate，IL-10 level， SOD and CAT activities， and protein expressions of HIF-1α， VEGF， and VEGFR-2， with statistically significant differences （P＜0.05）. YC-1 partially reversed the improvement effects of baicalin on angiogenesis and inflammation in DFU rats （P＜0.05）. Conclusion Baicalin can reduce inflammation and oxidative stress，promote angiogenesis，and accelerate wound healing in DFU rats by activating the HIF-1α/VEGF signaling pathway.

R285.5

武汉市医学科研项目（编号：WZ20C07）