Induction And Mechanism Of Phospho-p53 Protein Activation In Rat Hippocampus Following Forebrain Ischemia-Reperfusion Model

In the present study, the rats were subjected four-vessel occlusion (4-VO) with some modification. To assess the model was whether validated or not with electroencephalogram (EEG). The changes of phospho-p53 protein level in the hippocampus of the rats were examined with Western Blot. Ketamine is a antagonist of N-methyl-D-aspartate(NMDA) receptor calcium channel, and Nifedipine is a antagonists of L-voltage sensitivity calcium channel(L-VSCC). The study aim is to find out the roles of the two drugs in phospho-p53 protein activation.Results: (1)the model of forebrain ischemia with four-vessel occlusion was tested with EEG, the brainwave of the sham-operated rat was big and frequent, the brainwave of the producing ischemic rat almost was a straight line.After reperfusion 30min-60min, the brainwave of the experimental rat resumed. (2)The activation of phospho-p53 protein was increased after reperfusion, the level of experiment was 149% contray the contral's,the peak at 3d.AT 4d,the level decreased rapidly and reached the level of 1d. (3) Nifedipine and Ketamine could inhibit the level of phospho- p53 protein and the role depended on the dose of drug. 20mg/kg and 10mg/kg dose of Nifedipine could inhibit the induction of phospho-p53 protein distinctly, but the role of 5mg/kg dose was very small. (4) 50mg/kg and 25mg/kg dose of Ketamine could inhibit the activation of p53 protein and 12.5mg/kg dose only inhibited the p53 protein expression little .The solvents of Nifedipine and Ketamine almost couldn't inhibit the phospho-p53 protein activation.Conclusion: The induction level of phospho-p53 protein(serine 15)activation, in rat hippocampus following forebrain ischemia-reperfiision model was increasing at deferent time, the peak reached 3d.. Ketamine and Nifedipine could inhibit the induction level of phospho-p53 protein activation. Results indicated that NMDA receptor calcium channel and L-VSCC might take part in mechanism of phospho-p53 protein activation in rat hippocampus following forebrain ischemia-reperfusion and suggest the signal passagewayof NMDA receptor calcium channel/ L-VSCC-phospho-p53 protein(serine 15) activation may join in the neuronal damage after ischemia-reperfusion.