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海马区Ku70表达的影响  

Effects of extracellular signal-regulated kinase 1/2 on Ku70 protein expression in hippocampus of diabetics rats after cerebral ischemic reperfusion injury

作　　者：赵雅宁[1] 乔娇[1] 李建民[1] 常学优[1] 刘乐[1] 陈长香[1] 李淑杏[1] 

机构地区：[1]河北联合大学康复医学院神经研究所,唐山063000

出　　处：《中国糖尿病杂志》2014年第9期836-840,共5页Chinese Journal of Diabetes

基　　金：河北省自然科学基金(H2012401007);河北省卫生厅重点课题(ZD2010106)

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。分别于缺血灌注1、6、24、48h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再灌注(DCI)组1、6、24、48h存活神经细胞数量[(26.90±2.30)、(20.26±2.00)、(18.78±2.06)、(16.60±1.70)个/视野]低于血糖正常全脑缺血再灌注(NI/R)组[(30.22±2.28)、(26.00±1.23)、(24.80±2.17)、(18.20±1.48)个/视野],磷酸化ERK1/2和Ku70表达水平低于NI/R组(P<0.05)。应用U0126处理后,存活神经细胞数量及磷酸化ERK1/2和Ku70表达水平NI/R组低于DCI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。Objective To explore the regulation 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 was established by streptozocin(STZ)induction combined with improved pulsinelli's four-vessel occlusion.ERK1/2inhibitor U0126 was used to pretreatment the global cerebral ischemia in diabetic rat.At 1,6,24 and 48hours after cerebral ischemia-reperfusion,changes of neuron pathology were observed by electron microscope and light microscopy,and the phosphorylated ERK1/2and Ku70 expressions were detected by Western blot. Results(1)At 1,6,24 and 48hours after cerebral ischemia-reperfusion,the density of survival nerve cell in the diabetic cerebral ischemiareperfusion(DCI)group[(26.90±2.30),(20.26±2.00),(18.78±2.06),(16.60±1.70)number/visual fields]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)number/visual fields].The phosphorylated ERK1/2and 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 ERK1/2and Ku70 protein level was significantly lower in the U0126 group than in the DCI groups(P<0.05). Conclusion The decreased activity of ERK1/2and Ku70 protein participates and mediates the diabetes,which aggravates neuronal injury in diabetes rats after cerebral ischemia reperfusion.The decline of ERK1/2activity reduces the express of Ku70-bax,which leads to more nerve cell damages.

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 

分 类 号：R587.2[医药卫生—内分泌] R743.3[医药卫生—内科学]