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 细胞外调节蛋白激酶磷酸化对糖尿病全脑缺血再灌注大鼠后海马区Ku70表达的影响

来自:中国糖尿病杂志  编辑: 赵雅宁 乔娇 李建民 常学优 刘乐 陈|点击数:|2014-09-24

 ·糖尿病基础研究·

  【摘要】 目的 探讨细胞外调节蛋白激酶(ERK1/2)磷酸化对糖尿病全脑缺血再灌注大鼠后海马区Ku70表达的影响。 方法 采用STZ诱导联合改良Pulsineli 4血管阻断(4-VO)法制备糖尿病全脑缺血再灌注模型,应用ERK1/2抑制剂U0126对糖尿病全脑缺血再灌注大鼠预处理。分别于缺血1、6、24、48 h应用光镜和电镜观察海马区神经细胞形态变化;免疫印迹法检测磷酸化ERK1/2和Ku70表达水平。 结果 糖尿病全脑缺血(NI/R)组1、6、24、48 h存活神经元密度(26.90±2.30)、(20.26±2.00)、(18.78±2.06)、(16.60±1.70)低于血糖正常脑缺血(DCI)组(30.22±2.28)、(26.00±1.23)、(24.80±2.17)、(18.20±1.48),磷酸化ERK1/2和Ku70表达水平低于DCI组(P<0.05)。应用U0126处理后,存活神经元密度及磷酸化ERK1/2和Ku70表达水平NI/R组低于NI/R组(P<0.05)。 结论 ERK1/2活性及Ku70表达的降低,参与并介导了糖尿病,加重全脑缺血再灌注后神经细胞的丢失。糖尿病加重全脑缺血再灌注神经细胞损伤机制中,ERK1/2活性降低使Ku70表达减少,神经细胞丢失严重。

  【关键词】 糖尿病;再灌注损伤,脑缺血; 细胞外信号调节激酶; Ku70; 大鼠

  【Abstract】 Objective To explore the regulation effect of extracellular signal regulated kinase 1/2(ERK1/2) on Ku70 protein in hippocampus of diabetics rats after cerebral ischemic. Methods Global cerebral ischemia model in diabetic rat established by induction of streptozocin (STZ) combined with improved pulsinelli's four-vessel occlusion method. ERK1/2 inhibitor U0126 was used to pretreatment the global cerebral ischemia in diabetic rat. After 1,6,24 and 48 hours,changes of neuron pathology were observed by electron microscope and light microscopy, and the phosphorylated ERK1/2 and Ku70 expressions were detected by western blot. Results (1)The density of survival neurons in the diabetic cerebral ischemia-reperfusion (DCI)group[(26.90±2.30),(20.26±2.00),(18.78±2.06),(16.60±1.70)] was significantly lower than that in the normoglycemia global cerebral ischemia-reperfusion (NI/R) groups[(30.22±2.28),(26.00±1.23),(24.80±2.17),(18.20±1.48)]. The phosphorylated ERK1/2 and Ku70 levels were significantly lower in DCI group than in the NI/R groups(P<0.05);(2)The density of survival neurons and the phosphorylated ERK1/2 and Ku70 protein level was significantly lower in the U0126 group than in the DCI groups (P<0.05). Conclusion The activity of ERK1/2 and Ku70 protein decreasing participate and mediate the diabetic, which aggravate neuronal injury in diabetes rats after cerebral ischemia reperfusion. The decline of ERK1/2 activity reduces the express of Ku70-bax,leading to more nerve cell damages.

  【Key words】 Diabetes; Reperfusion Injury, brain ischemia; Extracellular signal-regulated kinase 1/2;Ku70; Rats

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