[1]张建忠,景丽,郭风英,等.磷酸化细胞外信号调节蛋白激酶加重糖尿病大鼠脑缺血性损伤[J].陆军军医大学学报(原第三军医大学学报),2007,29(24):2339-2342.
　ZHANG Jian-zhong,JING Li,GUO Feng-ying,et al.Phosphorylation of extracellular signalregulated protein kinase induced neuronal death under brain ischemia in diabetic rats[J].J Amry Med Univ (J Third Mil Med Univ),2007,29(24):2339-2342.
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磷酸化细胞外信号调节蛋白激酶加重糖尿病大鼠脑缺血性损伤(/HTML )
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陆军军医大学学报（原第三军医大学学报）[ISSN:1000-5404/CN:51-1095/R]

卷:
29卷
期数:
2007年第24期
页码:
2339-2342
栏目:
论著
出版日期:
2007-12-30

文章信息/Info

Title:
Phosphorylation of extracellular signalregulated protein kinase induced neuronal death under brain ischemia in diabetic rats
作者:
张建忠; 景丽;  郭风英; 马轶; 王一理
宁夏医学院病理学教研室；西安交通大学生命科学与技术学院免疫病理研究室
Author(s):
ZHANG Jian-zhong;  JING Li;  GUO Feng-ying;  MA Yi;  WANG Yi-li
Department of Pathology, Ningxia Medical College;Institute of Immunopathology, School of Life Science & Technology, Xi’an Jiaotong University
关键词:
脑缺血; 高血糖; 丝裂原激活蛋白激酶; 细胞外信号调节蛋白激酶; 糖尿病
Keywords:
cerebral ischemia;  hyperglycemia;  mitogenactivated protein kinase;  extracellular signal-regulated kinase;  diabetes
分类号:
R363;R587.1;R743.31
文献标志码:
A
摘要:
目的  探讨高血糖加重脑缺血性损伤的分子机制。  方法  采用大鼠全脑缺血模型，通过免疫组化、末端脱氧核苷酸转移酶介导的dUTP原位切口末端标记方法和Western blot 技术，对比研究Streptozotocin诱导的糖尿病大鼠脑缺血时神经元细胞外信号调节蛋白激酶1/2（ERK1/2）磷酸化和神经元凋亡的关系。  结果  糖尿病组脑缺血30 min和再灌注1、3、6 h后，扣带皮质和海马CA3区ERK1/2阳性细胞数和神经元凋亡明显高于正常血糖组（P<0.05）。ERK1/2抑制剂U0126可明显减少ERK1/2的磷酸化和凋亡神经元的数量。Western blot分析可见，在缺血脑组织中磷酸化ERK1/2明显增高，再灌注3和6 h糖尿病组显著高于正常血糖缺血组（P<0.05）。  结论  糖尿病高血糖加重缺血性脑损伤与MAPK家族激活有关，特别是ERK1/2参与了脑细胞的损伤。
Abstract:
Objective  To investigate the molecular mechanism of hyperglycemia on brain damage caused by ischemia.   Methods  Sixty-five male SD rats were divided into normoglycemia+ischemia group (n=20), diabetes+ischemia group (n=20), diabetes+ischemia+U0126 group (n=20) and normal control (n=5). Streptozotocin (60 mg/kg) was injected through vena caudalis to induce diabetes. The global cerebral ischemia was made by ligating bilateral common carotid arteries for 30 min and reperfusing for 1, 3, or 6 h. ERK inhibitor U0126 (4 g/kg) was injected through vena caudalis 30 min before ischemia, while normal saline was as substitute in other groups. The phosphorylation of ERK1/2 expression and neuronal apoptosis were studied by TUNEL, immunohistochemistry and Western blot.   Results  Increased phospho-ERK1/2 immunoreactive neurons in the cingulate cortex and hippocampal CA3 were detected in euglycemia+ischemia group. The number of phospho-ERK1/2 positive and apoptotic neurons was much more in diabetes+ischemia group than normoglycemia+ischemia group (P<0.05). Pretreatment with U0126 in diabetes+ischemia group significantly decreased ERK1/2 immunoreactive cells and apoptotic neurons. Western blot analysis confirmed that phospho-ERK1/2 increased significantly after ischemia and reperfusion as compared to normal controls. The amount of phospho-ERK1/2 was obviously increased after 3-hour or 6-hour reperfusion in diabetes+ischemia group in comparison with normoglycemia+ischemia group (P<0.05). Treatment with U0126 significantly reduced phospho-ERK1/2 in the diabetic rats.   Conclusion  ERK1/2 may play a role in mediating the apoptosis of neuronal cells under hyperglycemic condition.

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更新日期/Last Update: 2008-05-16