目的 观察丹蛭降糖胶囊干预后,2型糖尿病大鼠尿液内源性代谢物的变化,从代谢组学角度探究其防治2型糖尿病的作用机制。方法 SD大鼠随机分成对照组、模型组和丹蛭降糖胶囊组,造模大鼠以高脂饲料喂养4周后,ip小剂量链脲佐菌素(STZ 35 mg/kg)复制2型糖尿病模型。造模成功后,丹蛭降糖胶囊组ig丹蛭降糖胶囊(1.26 g/kg)4周,每周监测血糖。治疗结束,收集大鼠尿液,处死大鼠,腹主动脉取血测血浆胰岛素(INS)和糖化血红蛋白(GHb)水平。采用UPLC/QTOF-MS技术结合主成分分析(PCA)方法分析其尿液代谢谱变化,鉴定差异化合物,分析相关代谢通路。结果 血糖监测和INS、GHb检测结果表明,丹蛭降糖胶囊可以降低血糖,升高血浆中INS水平。在正、负离子模式下分别筛选出7个和6个差异性标志物。差异性标志物分别与糖代谢、酪氨酸代谢、色氨酸代谢和氧化应激反应等有关。结论 丹蛭降糖胶囊可以降低2型糖尿病大鼠血糖,修复胰岛细胞,其作用机制可能与调节能量代谢、酪氨酸代谢、色氨酸代谢和氧化应激状态相关。

Objective To observe the metabolic profile changes caused by Danzhi Jiangtang Capsule (DJC) in treatment of type 2 diabetic rats and to study the possible metabolism. Methods All the SD rats involved in the experiment were randomly divided into normal control, model, and DJC groups. The rats in the model and DJC groups were fed on high-fat diet for 4 weeks after ip injection with a small dose of streptozotocin to copy type 2 diabetic rat model. After the modeling, the rats in the DJC group were ig administered with DJC (1.26 g/kg) for 4 weeks, and the blood glucose was monitored weekly. After the treatment, urine of rats was collected, then all the rats were sacrificed, abdominal aortic blood was taken to detect the levels of insulin (INS) and glycated hemoglobin (GHb) in plasma. Using UPLC/QTOF-MS with principal component analysis (PCA) to analyze the metabolic profile changes, the metabolites were identified by databases, and metabolism pathways were analyzed. Results Blood glucose monitoring and INS, GHb testing results showed that DJC could lower blood sugar and elevate plasma INS level. In the positive and negative ion modes, we screened seven and six variability markers respectively. The variability markers were related to glucose metabolism, tyrosine metabolism tryptophan metabolism, and oxidative stress-related reactions. Conclusion DJC can lower blood sugar, repair islet cells to cure the type 2 diabetes, and the possible mechanism may relate to the regulation of energy metabolism, tyrosine metabolism, tryptophan metabolism, and oxidative stress.

国家中医临床研究基地业务建设科研专项课题(JDZX2012003);科技部重大新药创制项目(2010ZX09102-209)