The Primary Research Of P-ERK Mediateing The Apoptosis Of Astrocyte In Hyperglycemia-aggravated Ischemic Reperfusion Brain Injury

Objective We studied the apoptosis of astrocytes and the expression of activation of p-ERK,p-MEK and cPLA2 in the cortex and hippocampal CA4 region in the global cerebral ischemia-reperfusion rat models, and explored the molecular mechanism of hyperglycosemia- aggravated ischemic brain injury.Methods Spraggue Dawle rats were randomized into four groups:①Sham operation groups(Sham);②Normoglycemic cerebral ichemia groups(NCI);③Diabetes cerebral ichemia groups(DCI)。The making method of global cerebal ischemia model: ligated bilateral carotid artery and withdraw blood. Each ischemic group divided into four sub-groups, ischemia 15min, reperfusion 1h, 3h, 6h. Histopathology, TUNEL, Immunohistochemistry, Western blotting techniques methods were used to observe the information of astrocyte apoptosis and the phosphorylation of ERK,MEK1/2 and cPLA2 in cortex and hippocampal CA4 region.Result (1) astrocytes apoptosis of brain: In the NCI groups the majority of astrocytes happen apoptosis, and with the reperfusion time extended most models gradually increased in the number of apoptotic cells in the cortex and hippocampus CA4 region. Compared with the Sham and NCI groups, the number of apoptotic astrocyte in the DCI groups markedly increased in the cortex and hippocampus CA4 region.(2) Phosphorylation of ERK1/2 by immunohistochemistry:In the NCI groups we found phospho-MEK1/2 had a little expressed at different time points, there was no difference compared with the Sham groups. In the DCI groups global cerebral ischemia medols at 15 minutes after ischemia and 1,3,6-hour after reperfusion in cortex and hippocampal CA4 region, astrocytes mostly happen apoptosis,and higher than the Sham and NCI groups.(3) Phosphorylation of MEK1/2 by immunohistochemistry:In the NCI groups we found phospho-ERK1/2 had a little expressed at different time points,and higher than the Sham groups. In the DCI groups global cerebral ischemia medols at 15 minutes after ischemia and 1,3,6-hour after reperfusion in cortex and hippocampal CA4 region, astrocytes mostly happen apoptosis,and expressed highly at 6 hour reperfusion in cortex,at 3 hour reperfusion in hippocampal CA4 region,higher than the Sham and NCI groups.(4)Immunohistochemical results of cPLA2: In the NCI groups we found cPLA2 had a little expressed at different observed time points, there was no difference compared with the Sham groups.In the DCI groups the expression of cPLA2 increased slightly compared with Sham and NCI groups.Conclusions (1) Diabetes-induced hyperglycaemia can aggravate the injury of the cortex and hippocampal CA4 region ,as cerebral ischemia-reperfusion.(2) The increased apoptotic nerve cell and astrocytes were participated in the injury of cortex and hippocampal CA4 in diabetes-induced hyperglycaemia cerebral ischemia.(3) The astrocytes apoptosis can aggravate the brain injury through advanced nerve cell apoptosis in diabetes-induced hyperglycaemia cerebral ischemia.(4)ERK1/2 can induced the increased apoptosis of nerve cell and astrocytes in cortex and hippocampal CA4 in hyperglycaemia cerebral ischemia.(5) As diabetes-induced hyperglycaemia cerebral ischemia, the activation of p-ERK,MEK and cPLA2 incrased. This may be related to the incrase of astrocytes apoptosis in the cortex and hippocampal CA4.