摘要目的：探讨异丙酚减轻氯胺酮麻醉对幼年大鼠海马神经元和认知功能损害机制。方法将80只日龄7 d的SD大鼠随机分为生理盐水组（NS）、氯胺酮70 mg/kg组（K组）、氯胺酮70 mg/kg+异丙酚35 mg/kg组（P+K低剂量）、氯胺酮70 mg/kg+异丙酚70 mg/kg组（P+K高剂量），每组20只，均腹腔注射相应药物1 ml，间隔2 h再次注射，维持6 h。麻醉结束后各组随机选取10只处死，取幼鼠海马脑组织制作切片，测定海马CA1区神经元细胞凋亡情况、海马CA1区半胱氨酸天冬氨酸特异性蛋白酶?3（Caspace?3）蛋白及海马神经元苏氨酸231位点磷酸化tau蛋白（Tau?pThr231）、丝氨酸4.4位点磷酸化tau蛋白（Tau?pSer404）表达，各组余下幼鼠饲养21 d后进行水迷宫实验。结果与P+K低剂量组、P+K高剂量组、NS组相比，K组第3 d潜伏期时间（98.64±15.63比81.26±5.69、64.17±4.26、51.97±13.26）增加（P<0.05），穿越平台次数（6.18±2.26比1.34±0.29、3.51±1.03、4.97±1.35、6.18±2.26）减少（P<0.05），神经细胞凋亡率（13.15±4.02比8.02±2.34、4.18±2.02、2.64±1.86）、海马CA1区Caspace?3蛋白表达（16.52±2.67比11.36±1.86、5.65±1.03、5.65±1.03）、海马神经元Tau?pThr231蛋白表达（59.94±8.69比47.26±7.26、35.06±7.29、30.05±5.06）均增加（P<0.05），P+K高剂量组、NS组穿越平台次数、神经细胞凋亡率、海马CA1区Caspace?3蛋白表达、海马神经元Tau?pThr231蛋白表达相比差异无统计学意义（P>0.05）；4组海马神经元Tau?pSer404蛋白表达差异无统计学意义（P>0.05）。结论异丙酚可减轻氯胺酮麻醉所致幼年SD大鼠神经元和认知功能损害，机制可能为抑制Caspace?3蛋白表达上调、Tau磷酸化及降低神经细胞凋亡。

abstractsObjective To investigate the mechanism by which Propofol alleviates Ketamine anesthesia induced injury in hippocampal neurons and cognitive function of young rats. Methods Eighty 7?day?old SD rats were randomly divided into the normal saline(NS)group,Ketamine 70 mg/kg group(K group),Ketamine 70 mg/kg+Propofol 35 mg/kg(P+K low dose)group,Ketamine 70 mg/kg+Propofol 70 mg/kg (P+K high dose) group (n=20 each). All rats received 1 mL corresponding drugs via intraperitoneal injection,with the 2 h dosing interval,and maintained for 6 h. After anesthesia,10 rats in each group were randomly selected and executed. The hippocampal tissues from the rats were taken for section. The hippocampal CA1 neuronal cell apoptosis,hippocampal CA1 cysteinyl aspartate?specific proteinases?3 (Caspace?3)protein,hippocampal neurons threonine 231 site phosphorylation tau protein(Tau?pThr231), and serine 4.4 site phosphorylation tau protein (Tau?pSer404) expression were measured. The remaining young rats in each group were fed for 21 d,then underwent water maze test. Results Compared with the P+K low dose group,P+K high dose group and NS group,the latency time at 3 d in the K group(98.64±15.63 vs 81.26 ± 5.69,64.17 ± 4.26,51.97 ± 13.26)was increased(P<0.05),the times of crossing the platform (6.18 ± 2.26 vs 1.34 ± 0.29,3.51 ± 1.03,4.97 ± 1.35,6.18 ± 2.26)were decreased(P<0.05),and the rate of neural apoptosis(13.15±4.02 vs 8.02±2.34,4.18±2.02,2.64±1.86),hippocampal CA1 Caspace?3 protein expression(16.52±2.67 vs 11.36±1.86,5.65±1.03,5.65±1.03),hippocampal neurons Tau?pThr231 protein expression(59.94±8.69 vs 47.26±7.26,35.06±7.29,30.05±5.06)were all increased(P<0.05). There were no significant differences in the times of crossing the platform,rate of neural apoptosis,hippocampal CA1 Caspace?3 protein expression and hippocampal neurons Tau?pThr231 protein expression between the P+K high dose group and NS group(P>0.05). There was no significant difference in ther hippocampal neurons Tau?pSer404 protein expression among the four groups (P>0.05). Conclusion Propofol can reduce Ketamine anesthesia induced injury in hippocampal neurons and cognitive function of young SD rats. Its mechanism may be inhibiting the up?regulation of Caspace?3 protein expression and Tau phosphorylation, and reducing neuronal apoptosis.