The Influence Of Ca～(2+) On The Phosphorylation Of CREB, And The Relationship Between P-CREB And Apoptosis Neurons In Neonatal Rats After Hypoxic-ischemia

BACKGROUND:Hypoxic-ischemic encephalopathy(HIE) is a common complication in perinatal stage,it is mainly caused by suffocation which leads to hypoxic-ischemic brain damage(HIBD). HIBD can damage the quality of life and health of newborns, even leave severe sequelae such as Epilepsy, cerebral palsy etc,or result in newborn death . The machanism of HIBD is not definite. In past time , studies were mainly concentrated on the machanism of neron apopotosis triggered by the influent of Ca2+ after hypoxic-ischemia(HI). In recent time , some studies made domestically and abroad explored the influence of CREB(c~AMP response element binding protein) on HIBD , and indicated that P-CREB(phosphorylated CREB or activated CREB)can prohibit neuron apoptosis and stimulate neuron restoration after hypoxic-ischemic brain damge.Other studies report that the influent of Ca2+ after hypoxic-ischemia can influence the phosphorylation of CREB. This experiment was intended to find the influence of Ca2+ on thephosphorylation of CREB after HIBD in order to get acquainted with the effect of the influent of Ca2+on neuron damage after HIBD, and evaluate the value of Ca2+ antagonist in the therapy of HIE. AIM:To explore the influence of Ca2+ on the phosphorylation of CREB and apoptosis of neurons in the neona tal rats brain after hypoxic-ischemia(HI) and to offer some theoretical basis for the therapy of HIBD in clinic. METHODS:Seven days old SD rats (n=126) were randomly divided into three groups : sham control group, HI group; and the Ca2+ antagonist+ HI group (intervenient group). In the HI group and intervenient groups , the right common carotid artery was occluded for 2 h by No 0 thread, then exposed to 80mL L-1 oxygen and 920mL L-1 nitrogen gas mixture for 2 h . In the intervenient group, Nimodipine was injected into the abdominal cavity before and after HI respectively. In different time periods after HI, the expression of P-CREB in rat right hippocampus of different groups was detected by immunohistochemical methods. The apoptosis neurons in rat right hippocampus of different groups is detected by TUNEL method. RESULTS:In the HI group, the expression of P-CREB in the right hippocampus was much higher than that in the sham control group (p<0. 01), and peaked at 4 hs after HI, and then decreased gradually ; The number of apoptosis neurons inthe right hippocampus was much higher than that in the sham control group (p<0.01), This number peaked at 48hs after HI, and then decreased progressively. In the intervenient group, the expression of P-CREB had no significant reduction compared with HI group (p>0. 05) , but the number of apoptosis neurons were much fewer than HI group (p