DL-炔丙基甘氨酸对2型糖尿病大鼠胰岛β细胞功能和凋亡相关蛋白的影响  

Effects of DL-propargylglycine on isletβ-cell function and apoptosis-related proteins in type 2 diabetic rat

作　　者：胡军[1] 朱琳[1] 杨少娟[1] 许腾[1] 高啸[1] 鲁向明[2] 李安意[3,4] 

机构地区：[1]华中科技大学同济医学院附属梨园医院内分泌科,湖北武汉430077 [2]华中科技大学同济医学院附属梨园医院肿瘤科,湖北武汉430077 [3]华中科技大学同济医学院附属梨园医院 [4]华中科技大学同济医学院附属同济医院实验动物学部,湖北武汉430030

出　　处：《中国医院药学杂志》2015年第8期705-709,共5页Chinese Journal of Hospital Pharmacy

基　　金：湖北省自然科学基金资助项目(编号:2012FFB02317)

摘　　要：目的:探讨硫化氢(H2S)合成酶抑制剂DL-炔丙基甘氨酸(PAG)对其2型糖尿病(T2DM)大鼠胰岛β细胞功能和凋亡相关蛋白的影响。方法:采用高糖高脂饮食喂养和腹腔注射小剂量STZ的方法建立大鼠T2DM模型,将成模大鼠按随机数字表法随机分为糖尿病组(DM组),糖尿病+DL-炔丙基甘氨酸组(DM+PAG组),另设正常对照组,各15只。每日固定时间腹腔注射受试制剂,DM+PAG组给予PAG[50 mg/(kg·d)],对照组和DM组给予相同体积的生理盐水,连续给药2周。投药结束后,检测各组大鼠空腹血糖(FBG)、血浆胰岛素(FIns)水平,胰腺组织中H2S水平,免疫组化法检测分析胰腺组织胰岛素、Caspase-3、Bax和Bcl-2的表达情况,并计算胰腺组织相对β细胞数量和平均β细胞面积。结果:与对照组相比,DM组大鼠血浆FIns降低,FBG升高,胰腺组织H2S浓度水平升高;胰腺组织胰岛素阳性颗粒减少,Caspase-3、Bax表达增强,Bcl-2的表达减弱,Bc1-2/Bax比值降低;相对β细胞数量和平均β细胞面积均明显减小;经PAG处理后,大鼠血浆FIns明显升高,FBG降低,胰腺组织H2S浓度明显降低;胰腺组织胰岛素阳性颗粒明显增多,Caspase-3、Bax表达减弱,Bcl-2的表达增强,Bc1-2/Bax比值升高;相对β细胞数量和平均β细胞面积增加。结论:内源性H2S通过调节胰岛β细胞凋亡相关蛋白表达,促进胰岛β细胞的凋亡,减少2型糖尿病大鼠胰岛β细胞的相对数量,从而减少胰岛素的分泌;而PAG能减少胰岛β细胞凋亡,增加2型糖尿病大鼠胰岛β细胞的相对数量,增加胰岛素的分泌,达到控制血糖的目的。OBJECTIVE To investigate the effects of DL-propargylglycine （PAG） , a hydrogen sulfide （H2S） synthetase in- hibitor, on islet 13-cell function and apoptosis-related proteins in type 2 diabetic rat model. METHODS High glucose ＆ high fat diet and low-dose intraperitoneal injection of STZ method were used to establish T2DM rat model. The model rats were ran- domly divided into DM group, DM ＋ PAG group, a normal control group was also assigned. Each group included 15 animals. Fixed time daily intraperitoneal injection of test preparation was administered. DM ＋ PAG group was given PAG （50 mg·kg^-1·d^-1 ）, control and DM groups were given saline of equal volume for 2 weeks continuously. The serum levels of fasting blood glucose （FBG） and insulin （Fins）, hydrogen sulfide （H2S） concentrations in pancreatic tissues were measured. Insulin, Caspase -3, Bax and Bcl-2 were detected by immunohistochemistry in pancreatic tissues. And relative β mass and the average is let β cell area were calculated. RESULTS Compared with control group, plasma FBG and H2S concentrations in pancreatic tis- sues increased （P〈0. 05）, plasma Fins decreased （P〈0. 05） in DM group. Pancreatic insulin-positive granules were reduced, expression of Caspase-3 and Bax increased, Bcl-2 and Bcl-2/Bax ratio decreased; the relative 13 mass and the average β cell area decreased significantly. Compared with DM group, plasma FBG and H2S concentrations in pancreatic tissue significantly de- creased （P〈0. 05）, plasma Fins significantly increased （P〈0. 05） in DM ＋ PAG group. Pancreatic insulin-positive granules increased, and expression of Caspase-3 and Bax decreased, Bcl-2 and Bcl-2/Bax ratio increased; the relative β mass and the av- erage β cell area increased significantly. CONCLUSION H2 S can promote apoptosis of pancreatic β cells by regulating apopto- sis-related protein expression in pancreatic, reducing the relative number of islet β cells in type 2 diabetic rat, thereby reducing insulin secre

关 键 词：硫化氢 糖尿病 DL-炔丙基甘氨酸 凋亡蛋白 

分 类 号：R966[医药卫生—药理学]