靶向二肽基肽酶维药体外筛选模型的建立及应用  

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

作　　者：张晓翠[1,2] 赵海清[2] 窦君[2] 张富春[1] 阿吉艾克拜尔·艾萨[2] 

机构地区：[1]新疆大学生命科学与技术学院,新疆生物资源基因工程国家重点实验室培育基地,新疆乌鲁木齐830046 [2]中国科学院新疆理化技术研究所,干旱区植物资源化学重点实验室,新疆乌鲁木齐830011

出　　处：《新疆大学学报（自然科学版）》2014年第2期222-226,共5页Journal of Xinjiang University(Natural Science Edition)

基　　金：国家自然科学基金联合基金项目(U1203203)资助

摘　　要：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?C、反应时间30 min和竞争性抑制剂Ile-Pro-Ile浓度0.68mmol/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.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.

关 键 词：Ⅱ型糖尿病 维药 抑制剂 

分 类 号：Q946.8[生物学—植物学] R965.1[医药卫生—药理学]