目的  探讨当归内酯联合消渴丸对糖尿病肾病大鼠血糖调节、肾脏保护及其体内血管内皮生长因子（VEGF）信号通路的调节作用。  方法  75只大鼠随机分为5组，分别为对照组、模型组、消渴丸组、当归内酯组、当归内酯联合消渴丸组，每组15只。除对照组外，其余大鼠建立糖尿病肾病大鼠模型，消渴丸组、当归内酯组、当归内酯联合消渴丸组分别灌胃给予大鼠消渴丸（0.8 g/kg）、当归内酯（20 mg/kg）、消渴丸（0.8 g/kg）联合当归内酯（20 mg/kg），每日给药1次，连续8周后，测定大鼠24 h尿蛋白量、空腹血糖及餐后血糖水平、糖化血清蛋白及糖化血红蛋白水平、空腹胰岛素水平及胰岛素敏感指数、血肌酐（SCr）及血尿素氮（BUN）水平，Real-time PCR检测大鼠胰岛组织胰岛素（INS）及葡萄糖-6-磷酸酶（G6Pase）mRNA水平， HE染色检测大鼠肾脏组织病理学变化，Western blotting及免疫组织化学检测大鼠肾脏VEGF、血管内皮生长因子受体2（VEGFR2）水平。 

  结果  与模型组相比，当归内酯联合消渴丸大鼠24 h尿蛋白量、空腹血糖及餐后血糖水平、糖化血清蛋白及糖化血红蛋白水平、空腹胰岛素水平、SCr及BUN水平、肾脏组织VEGF、VEGFR2蛋白水平及相对积分吸光度均明显降低（P<0.05），胰岛素敏感指数、胰岛组织INS及G6Pase mRNA水平明显升高（P<0.05），差异有统计学意义，同时糖尿病肾病大鼠肾脏组织病理学明显改善。   结论  当归内酯联合消渴丸能够降低糖尿病肾病大鼠血糖水平，同时改善大鼠肾功能及病理变化，其机制可能与调节VEGF信号通路有关。

Objective  To investigate the effects of angelica lactone combined with Xiaoke pill on blood glucose regulation, renal protection and vascular endothelial growth factor signal pathway in diabetic nephropathy rats.     Methods  Totally 75 rats were randomly divided into control group, model group, Xiaoke pill group, angelica lactone group and angelica lactone combined with Xiaoke pill group, with 15 rats in each group. Except for the control group, the rest of the rats established diabetic nephropathy model. Rats in Xiaoke pill group, angelica lactone group and angelica lactone combined with Xiaoke pill group were given Xiaoke pill (0.8 g/kg), angelica lactone (20 mg/kg), Xiaoke pill (0.8 g/kg) combined with angelica lactone (20 mg/kg), respectively, once for 8 weeks. The levels of 24-hour urinary protein, fasting and postprandial blood glucose, glycosylated serum albumin and glycosylated hemoglobin, fasting insulin and insulin sensitivity index, serum creatinine (SCr) and urea nitrogen (BUN) were measured. The levels of insulin (INS) and glucose-6-phosphatase (G6Pase) mRNA in islet tissue were measured by Real-time PCR. Renal histopathological changes were detected by HE staining. The levels of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor 2 (VEGFR2) in rat kidney were detected by Western blotting and immunohistochemistry.    Results  Compared with the model group, 24-hour urinary protein, fasting and postprandial blood glucose, glycosylated serum albumin and glycosylated hemoglobin, fasting insulin, SCr and BUN, VEGF and VEGFR2 protein levels and relative integral absorbance of kidney tissue in angelica lactone combined with Xiaoke pill group were significantly lower than those in model group(P<0.05). The insulin sensitivity index, the levels of INS and G6Pase mRNA in islet tissue were significantly increased(P<0.05), and the renal histopathology of diabetic nephropathy rats was significantly improved.    Conclusion  Angelica lactone combined with Xiaoke pill can reduce blood glucose level, increase insulin sensitivity index, and its mechanism may be related to the regulation of VEGF signal pathway.