The effects of U0126 on extracellular signal regulated kinase1/2 and Ku70 protein in hippocampus of diabetic rats after cerebral ischemia/reperfuson injury / 中华急诊医学杂志

ABSTRACT

Objective To investigate the effects of inhibitors U0126 on expression of ERK1/2 and Ku70 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 immunohistochemistry method was used to detect the levels of phosphorylated ERK1/2 and Ku70 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 DCI + 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 inhibiting the activation of ERK1/2,thereby reducing the level of Ku70 protein in brain hippocampus of diabetic rats after global cerebral ischemia.