中文摘要：

目的研究二肽基肽酶4（dipeptidylpeptidase-d-，DPP-4）抑制剂对胰岛B细胞Bcl-2及Bax蛋白表达的调节作用是否通过增加胰腺组织中1氨基丁酸（^yaminoacidbutyricacid，GABA）含量这个途径实现。方法清洁级sD大鼠50只，随机选取10只为正常对照组。余40只采用高脂喂养联合链脲佐菌素（STZ）的方法诱导成糖尿病模型。随机分为3组：糖尿病对照组、DPP4抑制剂组、拮抗剂组（DPP4抑制＋GABA受体拮抗剂）。药物干预6周后检测血糖、血清胰岛素、胰升糖素的水平及胰岛B细胞中GABA、Bcl-2及Bax蛋白的表达情况。结果（1）DPP4抑制剂组与糖尿病对照组相比，血清胰岛素水平升高（P〈0．05），血糖水平降低（P〈0．05），血清胰升糖素水平降低（P〈0．05）。（2）拮抗剂组与DPP4抑制剂组相比，大鼠血清胰岛素水平降低（P〈0．05），血糖水平升高（P〈0．05），血清胰升糖素水平升高（P〈0．05）。（3）DPP--4抑制剂组与糖尿病对照组相比，大鼠胰岛p细胞GABA表达升高（P〈0．05），Bax蛋白表达降低（P〈0．05），Bcl-2蛋白的表达升高（P〈0．05）。（4）拮抗剂组与糖尿病对照组相比，大鼠胰岛B细胞GABA表达升高（P〈0．05），与DPP4抑制剂组相比，大鼠胰岛β细胞Bax蛋白表达升高（P〈0．05），Bcl-2蛋白的表达降低（P〈0．05）。结论DPP4抑制剂能够通过增加胰岛GABA表达来促进胰岛素分泌，减少胰升糖素分泌，增加胰岛β细胞抗凋亡蛋白Bcl-2的表达，降低胰岛β细胞促凋亡蛋白Bax的表达，抑制2型糖尿病大鼠胰岛β细胞的凋亡。

英文摘要：

Objective To explore the effects of dipeptidyl peptidase （ DPP-4 ） inhibitor on proteins expression of Bcl-2 and Bax of islet β-cells through increasing the expression of islet Y amino acid butyric acid （GABA）. Methods A total of 50 rats of clean grade were studied. Among them, ten rats were randomly selected as normal controls, the remaining forty rats were fed with high-fat diet and then intraperitoneal injection with streptozotocin, the diabetic rats models were then established. Rats were randomly divided into three groups： i. e. diabetic control group, DPP-4 inhibitor group, and antagonist group （ DPP-4 inhibitor and GABA receptor antagonist）. Six weeks later, blood glucose, serum insulin, glucagon, and the proteins expression of GABA, Bcl-2, and Bax of islet β-cells were measured. Results （ 1 ） Compared with diabetic control group, serum insulin was increased （ P〈0.05 ） , blood glucose and serum glucagon were decreased in DPP-4 inhibitor group （ P〈0. 05 ）. （ 2 ） Compared with DPP-4 inhibitor group, serum insulin was decreased （ P〈0.05 ） , blood glucose and serum glucagon were increased （ P〈0. 05 ） in antagonist group. （ 3 ） Compared with diabetic control group, the expression of GABA was increased （P〈 0.05 ） , the expression of Bcl-2 protein was increased （P 〈 O. 05 ） in pancreatic β-cells in DPP-4 inhibitor group. （4） Compared with diabetic control group, the expression of GABA in pancreatic β-cells was increased in antagonist group （P〈0. 05 ） . Compared with DPP-4 inhibitor group, the expression of Bax protein in pancreatic β-cells was increased in antagonist group（P〈0. 05 ） , while the expression of Bcl-2 protein was decreased （P〈 O. 05 ）. Conclusions DPP-4 inhibitor could increase the secretion of insulin, decrease the secretion of glucagon, up-regulate expression of anti-apoptosis protein Bcl-2, and down-regulate expression of apoptosis proteinBax in pancreatic β-cells through increasing the expression of GABA, in