| Background and objective:p63 gene is homologous to p53 gene,transcription into two subtypes:Tap63 and Np63,studies had found that they had pro-apoptotic and anti-apoptotic effect respectively,the balance between them had an important role in the regulation of apoptosis.The study found that p63 was the key proteins responsible for the neurons "helpful death" in the process of development of nervous system,and might participate in neurons apoptosis after cerebral ischemia.The studies had found p63 was high expression after cerebral ischemia/reperfusion in rats and had positive correlation with neuronal apoptosis,whether the expression of p63 increased after traumatic brain injury?The studies had found propofol had neuroprotective effect on brain injury,whether the apoptosis and p63 expression of neurons play a role in the neuroprotective effect?This experiment was designed to explore this question.In this study,the effect of propofol postconditioning on p63 protein,neuronal apoptosis in hippocampal CA1 area,CA3 area and cortex and the level of S100? in serum after traumatic brain injury were observed in rats,to explore the expression of p63 after traumatic brain injury and the role of p63 in neuroprotection of propofol postconditioning on traumatic brain injury,and to provide experimental evidence on drugs and methods which simulate the effect of p63 to regulate the neuronal apoptosis and play neuroprotective.Methods:seventy two male SD rats weighing 3 00?350g were randomly divided equally into three groups(n=24):sham operation group(N group),cerebral trauma group(T group),propofol postconditioning group(P group).The skulls were exposed in the rats of group N,without traumatic brain injury;group T for traumatic brain injury;traumatic brain injury model made by a free falling device;group Pwere injected propofol 100mg/kg by intraperi-toneal after traumatic brain injury,group N,T were received normal saline.The neurological severity scores was tested at 6h,24h,48h,7d after surgery respectively in all the rats.Under general anesthesia,all rats were executed and brain tissues were collected after perfused with 4%formaldehydum polymerisatum.The neuronal densities of hippocampal CA1 area,CA3 area and cortex were observed by HE staining,neuronal apoptosis indexes were determined by TUNEL,the expressions of p63 protein were detected by immuno-histochemistry(IHC)staining,and double antibody sandwich enzyme-linked immunosorbent assay(ELISA)were used for detecting the level of S100(3 in serum.Results:1.Neurological Severity Scores:There was no statistically significant of neurological severity scores at each time points after surgery in group A(p>0.05).The scores of group T,P decreased gradually after surgery,without statistically difference at 6h,24h after surgery in group T(p>0.05),and with statistically significant of scores at the rest time points within group T and all time points in group P(p<0.05).The scores of group T,P were higher than those in group N at the same time point after surgery(p<0.01),the scores of group P were lower than those in group T at 24h,48h,7d after surgery(p<0.05),without statistically significant at 6h after surgery between group T,P(p>0.05).2.Neuronal density:There was no statistically significant of neuronal densities of hippocampal CA1 area,CA3 area and cortex at each time points after surgery in group N(p>0.05).The neuronal densities of hippocampal CA1 area,CA3 area and cortex of group T,P decreased gradually at 6h,24h,48h after surgery,and then rose slightly at 7d after surgery,with statistically significant among all time points after surgery within the group T and P(p<0.05).The neuronal densities of hippocampal CA1 area,CA3 area and cortex of group T,P were lower than those in group N at the same time points after surgery(p<0.01),and the group P was higher than those in group N(p<0.05).3.The level of S1000? in serum:There was no statistically significant of the level of S100? in serum at each time points after surgery in group N(p>0.05).The level of S100? in serum of group T,P decreased gradually at 6h,24h,48h,7d with statistically significant among all time points after surgery within the group T and P(p<0.05).The level of S1000? in serum of group T,P were higher than those in group N at the same time points after surgery(p<0.01),and the group P was lower than those in group T(p<0.05).4.Neuronal apoptosis:Apoptotic neurons were very rare at each time points in group N after surgery,with no statistical significant(p>0.05).The neuronal apoptosis indexes of hippocampal CA1 area,CA3 area and cortex of group T,P rose gradually at 6h,24h,48h,and then decreased slightly at 7d,with statistically significant among all time points after surgery within the group T and P(p<0.05).The neuronal apoptosis indexes of group T,P were higher than those in group N at the same time points after surgery(p<0.01),and the group P was lower than those in group T(p<0.05).5.The expression of p63:The expression of p63 was very rare at each time in group N after surgery,with no statistical significant(p>0.05).The p63 positive cell rate of hippocampal CA1 area,CA3 area and cortex of group T,P rose gradually at 6h,24h,48h,and then decreased slightly at 7d,with statistically significant among all time points after surgery within the group T and P(p<0.05).The p63 positive cell rate of group T,P were higher than those in group N at the same time points after surgery(p<0.01),and the group P was lower than those in group T(p<0.05).6.Correlation analysis:The neuronal apoptosis had positive correlation with the expression of p63 and the level of S100? protein in serum.The expression of p63 had no correlation with the level of S100? protein in serum.Conclusion:1.The expression of p63 of hippocampal CA1 area,CA3 area and cortex increased after traumatic brain injury in rats,rose gradually at 6h,24h,48h,decreased slightly at 7d.2.The propofol postconditioning had neuroprotective effect after traumatic brain injury in rats,its mechanism could be related with the down-regulation of p63 gene and inhibiting apoptosis.3.The neuronal apoptosis had positive correlation with the expression of p63 and the level of S100? protein in serum.The expression of p63 had no correlation with the level of S100? protein in serum. |
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