U0126对糖尿病全脑缺血大鼠海马区细胞外信号调节激酶1／2和Ku70表达的影响  

The effects of U0126 on extracellular signal regulated kinasel/2 and Ku70 protein in hippocampus of diabetic rats after cerebral ischemia/reperfuson injury

作　　者：李建民[1] 赵雅宁[1] 景丽伟[1] 张盼[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, 河北省唐山063000

出　　处：《中华急诊医学杂志》2013年第9期983-988,共6页Chinese Journal of Emergency Medicine

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：目的探讨磷酸化细胞外信号调节激酶1／2（extracellularsignalregulatedkinase，ERKl／2）抑制剂U0126对糖尿病大鼠全脑缺血一再灌注后海马区ERKl／2和KuT0表达的影响。方法在河北联合大学神经外科中心实验室，采用链脲佐菌素诱导联合改良的Pulsineli4血管阻断（4一VO）法制作糖尿病全脑缺血一再灌注模型。80只雄性Sprague—Dawlley大鼠随机（随机数字法）分为假手术组（shamoperation，SO）、血糖正常全脑缺血一再灌注组（normoglycemiaischemia／reperfusion，NL／R）、糖尿病全脑缺血一再灌注组（diabetescerebralischemia，DCI）和DCI＋U0126干预组（尾静脉注射（0．01mg／kg）。各组分别在缺血1、6、24、48h取脑组织，HE染色检测海马区神经细胞形态变化；免疫组化法检测海马区磷酸化ERKl／2和Ku70表达水平。以SPSS17．0对实验数据进行统计分析，组间进行析因方差分析，P〈0．05为差异有统计学意义。结果与SO组比较，NI／R组大鼠海马区部分神经细胞出现变性坏死改变；磷酸化ERKl／2表达在1、6、24、48h显著增高（均P〈0．05）；Ku70表达在1h、6h显著增高（均P〈0．05），24、48h降低（均P〈0．05）；与NI／R组比较，DCI组脑组织形态结构损伤程度加重，1、6、24、48h磷酸化ERK1／2显著下降（均P〈0．05）；1、6、24、48hKu70显著下降（均P〈0．05）；与DCI组比较，DCI＋U0126组脑组织形态结构损伤程度加重，1、6、24、48h磷酸化ERK1／2显著下降（均P〈0．05）；1、6、24、48hKu70显著下降（均P〈0．05）。结论U0126通过抑制ERK1／2的激活、降低糖尿病全脑缺血大鼠海马区Ku70表达，加重对神经细胞有损伤作用。Objective To investigate the effects of inhibitors U0126 on expression of ERK1/2 and KuT0 in the hippocampus in diabetic rat after global cerebral ischemia and reperfusion. Methods The global cerebral ischemia model of diabetic rat was made by streptozotocin-induction with four-vessel occlusion of modified Pulsinelli＇s method. Adult male SD rats （n = 80） were randomly （random number） divided into 4 groups （n = 20 rats per group ）, namely sham operation （SO） group, normoglycemia ischemia/ reperfusion （NI/R） group, diabetes cerebral ischemia （DCI） group and DCI ＋ U0126 （0.01 mg/kg IV ） group. The morphological changes of neuronal cells were observed by using HE staining 1 h, 6 h, 24 h and 48 h after I/R; and immunohistoehemistry method was used to detect the levels of phosphorylated ERK1/2 and KuTO protein. Statistical analysis of experimental data was carried out by using SPSS 17.0 software. Comparisons between groups were done by using factorial variance analysis, and difference was statistically significant at P 〈 0. 05. Results Compared with SO group, some neurons showed histopathologic changes of neuronal necrosis and apoptosis in NI/R group as well as the phosphorylated ERK1/2 levels increased at 1, 6, 24, 48 h （P 〈 0. 05） ; The Ku70 levels increased at 1, 6 h （P 〈 0. 05 ） and were lower at 24 h, 48 h （P 〈 0. 05 ）; Compared with the NI/R group, the histopathological changes of brain tissue was more severe in DCI group, and the phosphorylated ERK1/2 levels were lower at 1, 6, 24, 48 h （P 〈 0. 05 ） ; The Ku70 protein levels were lower at 1, 6, 24, 48 h in DCI group （P 〈 0. 05 ） ; Compared with DCI group, the histopathological changes of neuronal necrosis and apoptosis was more severe in DC! ＋ U0126 group ; and the phosphorylated ERK1/2 expressions respectively decreased at 1,6, 24, 48 h （P 〈 0. 05） ; and the Ku70 protein levels were lower at 1, 6, 24, 48 h （ P 〈 0.05 ）. Conclusions U0126 enhanced the damage of nerve cells by inhibitin

关 键 词：大鼠 糖尿病 脑缺血-再灌注 丝裂酶原活化蛋白激酶 DNA依赖蛋白激酶 

分 类 号：R587.2[医药卫生—内分泌] R743[医药卫生—内科学]