中国组织工程研究

中国组织工程研究 ›› 2012, Vol. 16 ›› Issue (31): 5810-5816.doi: 10.3969/j.issn.2095-4344.2012.31.024

• 器官移植基础实验 basic experiments of organ transplantation • 上一篇    下一篇

肾缺血再灌注模型细胞凋亡与吡咯烷二硫代氨基甲酸的干预

李 丹，周海燕，张 伟，徐 岩   

  1. 青岛大学医学院附属医院肾内科，山东省青岛市 266003
  • 收稿日期:2012-01-12 修回日期:2012-01-29 出版日期:2012-07-29 发布日期:2012-07-29
  • 通讯作者: 徐岩，博士，主任医师，青岛大学医学院附属医院肾内科，山东省青岛市 266003
  • 作者简介:李丹★，青岛大学在读硕士，主要从事急性肾损伤方面的研究

Pyrrolidine dithiocarbamate effects on cell apoptosis in a model of renal ischemia/reperfusion injury

Li Dan, Zhou Hai-yan, Zhang Wei, Xu Yan   

  1. Department of Nephrology, Affiliated Hospital of Qingdao University Medical College, Qingdao 266003, Shandong Province, China
  • Received:2012-01-12 Revised:2012-01-29 Online:2012-07-29 Published:2012-07-29
  • Contact: Xu Yan, Doctor, Chief physician, Department of Nephrology, Affiliated Hospital of Qingdao University Medical College, Qingdao 266003, Shandong Province, China xuyan67@126.com
  • About author:Li Dan★, Studying for master’s degree, Department of Nephrology, Affiliated Hospital of Qingdao University Medical College, Qingdao 266003, Shandong Province, China lidan0823@163.com

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摘要：

背景：肾缺血/再灌注诱导产生大量活性氧，导致核因子κB的活化。激活的核因子κB通过调节诱导型一氧化氮合酶的生成，进而导致一氧化氮的大量产生和触发细胞凋亡。
目的：观察吡咯烷二硫代氨基甲酸对肾缺血再灌注后肾脏组织中核因子κB、诱导型一氧化氮合酶、一氧化氮、caspase-3和细胞凋亡指数的作用。
方法：将健康雄性Wistar大鼠随机分为3组：缺血再灌注组和吡咯烷二硫代氨基甲酸组通过右侧肾切除+左肾动脉夹闭 45 min建立肾缺血/再灌注模型，吡咯烷二硫代氨基甲酸组于实验前30 min尾静脉注射吡咯烷二硫代氨基甲酸 (100 mg/kg)。假手术组不给予缺血再灌注处理。
结果与结论：与假手术组相比，缺血再灌注组大鼠再灌注后肾组织核因子κB表达水平、血肌酐水平、尿素氮水平、诱导型一氧化氮合酶活性、一氧化氮表达水平、caspase-3表达水平和细胞凋亡水平增加(P < 0.05)；而与缺血再灌注组相比，吡咯烷二硫代氨基甲酸组大鼠再灌注后以上指标均好转。说明肾缺血/再灌注损伤可引起肾组织结构损伤和细胞凋亡，且与核因子κB引起的一氧化氮高表达有关；应用核因子κB抑制剂吡咯烷二硫代氨基甲酸可对缺血再灌注肾损伤发挥明显的保护作用。

关键词: 吡咯烷二硫代氨基甲酸, 核因子κB , 细胞凋亡, 肾脏, 大鼠

Abstract:

BACKGROUND: Renal ischemia/reperfusion (I/R) induces the generation of reactive oxygen species (ROS), which leading to activation of nuclear factor-kappa B (NF-κB). NF-κB regulates production of inducible nitric oxide synthase (iNOS), resulting in increased nitric oxide production and triggering apoptosis.
OBJECTIVE: To evaluate the potential protective effect of pyrrolidine dithiocarbamate effects on NF-κB, iNOS, nitric oxide, caspase-3 and cell apoptotic index in the kidney after I/R.
METHODS: Healthy male Wistar rats were randomly divided into three groups: I/R group: underwent 45 minutes of left renal ischemia and contralateral nephrectomy, established rats renal I/R model. Pyrrolidine dithiocarbamate (PDTC) group: rats were administered PDTC (100 mg/kg intravenous bolus 30 minutes prior to I/R). Sham group: no I/R management.
RESULTS AND CONCLUSION: Compared with sham group, NF-κB, serum creatinine, urea nitrogen, iNOS, nitric oxide, caspase-3 expression and apoptosis were increased (P < 0.05). Compared with I/R group, above-mentioned indices in the PDTC group were improved. These indicate that renal I/R injury could cause renal injury and apoptosis, which was associated with NF-κB induced high expression of nitric oxide. NF-κB inhibitor PDTC obviously protects renal I/R injury.

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