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[目的]探讨五子降糖方对二肽基肽酶Ⅳ(DPP-4)活性的影响,研究其发挥降糖作用的可能机制。[方法]选取SPF级雄性GK大鼠,适应性喂养1周后给予高脂饲料,连续喂养4周,测定血糖,以随机血糖>11.1 mmol/L或餐后2 h血糖(2 h PG)>16.7 mmol/L为成模标准,将成模2型糖尿病(T2DM)大鼠随机分为模型组、二甲双胍组(0.1 g/kg)、五子降糖方低、中、高剂量组(3.5、7.0、14 g/kg,折合生药量),同时另选Wstar大鼠为正常组,正常组与模型组灌胃等体积纯净水,灌胃前测定空腹血糖(FBG),灌胃后4周、8周测定FBG及2 h PG,8周后处死动物,检测血清C肽(CP)水平;采用发色底物法建立DPP-4抑制剂体外筛选模型,分别应用五子降糖方及其组方的各味单药菟丝子、女贞子、紫苏子、莱菔子、车前子水提物对DPP-4抑制剂体外筛选模型进行干预,以磷酸西格列汀片作为阳性对照药,测定A值,计算DPP-4抑制率,比较IC50差异。[结果]五子降糖方可降低T2DM大鼠FBG及2 h PG,增高血清C-P水平;对DPP-4抑制作用,五子降糖方IC50为(6 667.754±2 119.759)mg/L,其组成药物中莱菔子IC50为(382.554±7.750)mg/L,菟丝子IC50为(843.391±135.230)mg/L。[结论]五子降糖方可以降低T2DM FBG及2 h PG,改善胰岛β细胞功能,作用机制可能与DPP-4抑制作用有关,其中莱菔子、菟丝子可能是本方发挥DPP-4抑制作用的主要药物。
[Objective] To investigate the effect of Wuzi Jiangtangfang on the activity of DPP-4 and its possible mechanism of hypoglycemic effect. [Methods] SPF male GK rats were selected and fed with high-fat diet for 1 week after adaptive feeding. The rats were fed for 4 weeks continuously. Blood glucose was measured and the blood glucose> 11.1 mmol / L or 2 h postprandial blood glucose (2 h PG) 16.7 mmol / L was used as the standard of modeling. The T2DM rats were randomly divided into model group, metformin group (0.1 g / kg), low, middle and high doses of Wubi Hypoglycemic group (3.5, 14 g / kg, equivalent to crude drug volume). Meanwhile, Wstar rats were selected as the normal group. The normal group and the model group were given the same volume of pure water. Before the gavage, the fasting blood glucose (FBG), 4 weeks, The FBG and 2 h PG were determined and the animals were sacrificed 8 weeks later to detect the level of serum C-peptide (CP). The DPP-4 inhibitor screening model was established by chromogenic substrate method. A single drug dodder, Ligustrum lucidum, Perilla seed, Radish Seed, Psyllium extract DPP-4 inhibitors in vitro screening interventions, sitagliptin phosphate tablets as a positive control drug, determination of A value, DPP-4 inhibition rates were calculated and IC50 differences were compared. [Results] Wuzi Hypoglycemic could reduce FBG and 2 h PG in T2DM rats and increase serum CP level. IC50 of Wuzi HGP was (6 667.754 ± 2 119.759) mg / L for DPP-4 inhibition, and its composition The results showed that IC50 was (382.554 ± 7.750) mg / L and IC50 was 843.391 ± 135.230 mg / L. [Conclusion] Wuzi Hypoglycemic prescription can reduce T2DM FBG and 2 h PG, and improve the function of pancreatic β-cell. The mechanism may be related to the inhibition of DPP-4, of which Radix Rehmanniae Decoction and Dodder Seed may be the main inhibitory effect of DPP-4 drug.