靶向二肽基肽酶维药体外筛选模型的建立及应用

二肽基肽酶IV（dipeptidyl peptidaseIV，DPPIV）是治疗Ⅱ型糖尿病的新靶点，糖依赖性胰岛素释放肽和肠促胰岛素胰高血糖素样肽-1在体内有促进胰岛β细胞分泌胰岛素，胰岛素的生物合成，β细胞的生长并抑制其凋亡和抑制血糖升高等功能．二肽基肽酶Ⅳ可快速降解糖依赖性胰岛素释放肽和肠促胰岛素胰高血糖素样肽-1，使其失去生物活性．本实验利用Caco-2细胞中所得到的二肽基肽酶IV，优化酶活筛选体系．确定了二肽基肽酶Ⅳ最适底物Gly-Pro-pNA浓度为0.064 mg/mL、反应温度37℃、反应时间30 min和竞争性抑制剂Ile-Pro-Ile浓度0.68 mmol/L，从而建立了靶向二肽基肽酶Ⅳ的快速筛选体系．应用该模型，对18种维药提取物进行了筛选．本研究结果将为维药的进一步开发和利用提供了理论依据.

A Screening Model for Dipeptidyl Peptidase Inhibitorsin vitro and Its Application in Uyghur Medicine

Dipeptidyl peptidase IV（DPP Ⅳ） is a new target for treating type Ⅱ diabetes. Glucose-dependent insulin-releasing peptide, and the insulin glucagon-like peptide-1 could promote insulin secretion, biosynthesis, inhibit β-cell apoptosis, lower the blood sugar and other functions. DPP IV could degradate the level of glucose-dependent insulin-releasing peptide and glucagon-like peptide-1 to the loss of biological activity. Our experiment is to optimize the screening system for DPP IV inhibitors, based on DPP IV from Caco-2, results showed that the concentration of Gly-Pro-pNA is 0.064 mg/mL,reaction time is 30 minutes, temperature 37℃ and the concentration of IIe-Pro-IIe 0.68 mmol/L. Therely astablishing a rapid screening system of dipeptidyl peptidase. Application of the model 18 Uyghur herbal extracts were screened and some had the inhibitory activity of DPP IV. The study will provide support for further exploration and utilization of Uyghur herbs.