| Objective To investigate the effects of propofol on the expression of t PA,and whether propofol anesthesia leads to long-term learning and memory dysfunction in neonatal rats through affecting the expression of t PA and hindering the conversion of proBDNF to mBDNF in the hippocampus.Methods 162 SD rats of 7 d old weighted 12-16 g,sex in half,randomly divided into 3 groups(n=54): the rats in normal saline group(group C)were injected with 0.9 % NaCl for 7 days.The rats in single dose of propofol group(group SP)were injected with 0.9 % NaCl for 6 days and with propofol on the 7th day.The rats in repeated doses of propofol group(group RP)were injected with propofol for 7 days.All rats in each group were given intraperitoneal injection of propofol 75 mg/kg or 0.9 % NaCl 7.5 ml/kg.Blood glucose and blood gas analysis were tested of six rats in each group.The spatial learning and memory functions were determined by Morris water maze beginning in 17 d after the last injection.The morphological changes of the hippocampus were observed by HE staining and Nissl staining.The protein expression of tPA at 2 h,24 h,48 h,72 h,22 d after the last injection was tested by Western blot,and the mRNA expression of tPA was determined by RT-PCR.The protein expression of proBDNF、mBDNF、Caspase3 at 22 d after the last injection was detected by Western blot.Hippocampal neuron apoptosis was determined by TUNEL method.Results Compared with group C and group SP,the escape latency was prolonged,but the space exploration time and the number of crossing the original platform location were reduced in group RP(P<0.05);the protein expression of tPA in group RP was significantly decreased at each time point(P<0.05);the tPA mRNA expression was down-regulated obviously(P<0.05);the expression of tPA and mBDNF in group RP were declined,but the expression of proBDNF were higher(P<0.05);the number of nerve cells and nissl body in the hippocampus decreased,nerve cells arranged disorder and finally developed into neuronal degeneration and necrosis in group RP;the number of apoptotic neurons and the expression of cleaved-caspase3 were increased significantly,but the pro-caspase3 expression was reduced in group RP(P<0.05).But no significant difference between group SP and group C was observed(P>0.05)except the down-regulation of t PA protein expression at time point of 24 h(P<0.05).Conclusion Repeated doses of propofol leads to long-term cognitive dysfunction in neonatal rats,which may be related to the down-regulation of t PA expression,pro BDNF and mBDNF conversion disorder,neuronal normal morphology and function destruction,and the neuronal apoptosis in the hippocampus,whereas single dose of propofol has no significant effect. |
