基础医学与临床 ›› 2012, Vol. 32 ›› Issue (1): 36-41.

• 研究论文 • 上一篇    下一篇

吡咯烷二硫代氨基甲酸酯减轻2型糖尿病大鼠胰岛β细胞氧化损伤

丁海燕1,2,赵瑞景2,尹小妹1,1,刘桂红1,1,刘建坤1,1,朱铁年3   

  1. 1.
    2. 河北医科大学
    3. 中国人民解放军白求恩国际和平医院肿瘤科
  • 收稿日期:2010-12-27 修回日期:2011-06-27 出版日期:2012-01-05 发布日期:2011-12-28
  • 通讯作者: 朱铁年 E-mail:tienian_zhu@hotmail.com
  • 基金资助:
    吡咯烷二硫代氨基甲酸酯对糖尿病的治疗作用及其机制研究;PDTC对高糖"代谢记忆"血管损伤的防治作用;PDTC调控转录因子FoxO1活性对肝糖代谢的影响;吡咯烷二硫代氨基甲酸酯调控转录因子FOXO1对肝糖异生酶表达的影响

Pyrrolidine dithiocarbamate attenuates pancreatic β-cell oxidative injury in type 2 diabetic rats

  • Received:2010-12-27 Revised:2011-06-27 Online:2012-01-05 Published:2011-12-28

摘要: 目的 探讨吡咯烷二硫代氨基甲酸酯(PDTC)对2型糖尿病大鼠胰岛β细胞氧化损伤的影响及其机制。方法 用长期高脂饮食加小剂量链脲佐菌素(STZ,27mg/kg体重)建立2型糖尿病大鼠模型。PDTC治疗组大鼠每天腹腔注射PDTC(50mg/kg)1次,1周后取血浆检测血糖。取胰腺组织匀浆测定丙二醛(MDA)、超氧化物歧化酶(SOD)及谷胱甘肽过氧化物酶(GSH-PX)的含量;应用免疫组化和Western blot等检测胰腺组织中诱生型一氧化氮合酶(iNOS)的表达及硝基化酪氨酸(NT)的水平;流式细胞术检测胰岛β细胞凋亡百分率。结果 糖尿病大鼠血糖、MDA水平均显著高于对照组(P﹤0.01);SOD和GSH-PX水平明显低于对照组(P﹤0.01);胰岛组织中iNOS表达水平(0.37±0.06)和NT生成量(0.24±0.01)均较对照组(0.11±0.01)和(0.12±0.01)明显增多(P<0.01)。PDTC治疗后血糖明显降低,MDA明显减少(P<0.01);而SOD、GSH-PX水平明显升高(P<0.05,P<0.01);胰岛组织中iNOS表达及NT生成均明显减少(P<0.01);胰岛β细胞凋亡率明显降低(P<0.05)。结论 PDTC可以降低血糖,减轻大鼠体内氧化应激反应,减少糖尿病大鼠胰岛β细胞的凋亡。

关键词: PDTC, 糖尿病, 氧化损伤, 胰岛β细胞, 凋亡

Abstract: ABSTRACT: Objective To investigate the effect and mechanism of pyrrolidine dithiocarbamate (PDTC) on islet β cell oxidative injury in type 2 diabetic rats. Methods Type 2 diabetic rats model were set up by long-term feeding high-fat foods accompanied with a single intraperitoneal injection of low dose of streptozotocin (STZ, 27mg/kg body weight). The rats in PDTC group were administerd with PDTC (50mg/kg/d) by intraperitoneal injection. After treatment for 1 week, blood glucose levels were estimated. Malondialdehyde (MDA), Superoxide dismutase (SOD) and Glutathione peroxidase (GSH-PX) content in pancreatic tissue were measured. The expression of inducible nitric oxide synthase (iNOS) and the prouduction of nitrotyrosine (NT) in islet tissue were examined by using immunohistochemistry and Western blot. The rate of pancreatic islet β cell apoptosis was detected by flow cytometry. Results The blood glucose level, MDA content, pancreatic β-cell apoptosis, iNOS expression and NT production were significantly higher, while the SOD and GSH-PX activities were significantly lower in DM group than those in normal control group (P<0.01). After administration of PDTC, The level of blood glucose, MDA content, pancreatic β-cell apoptosis, iNOS expression and NT production were significantly decreased, while the SOD and GSH-PX activities were markedly increased when compared with DM group (P<0.01). Conclusion PDTC can reduce the level of blood glucose, relieve the oxidative stress reaction of diabetic rats, suppress the expression of iNOS and NT production, and decrease pancreatic islet β cell apoptosis in diabetic rats.

Key words: Pyrrolidine dithiocarbamate, Diabetes, oxidative injury, Pancreatic islet β cell, Apoptosis

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