CAJ | 학술논문

目的探讨不同剂量异丙酚麻醉对新生大鼠远期认知功能的影响.方法雄性SD大鼠100只,出生后7d,体重9～18g,采用随机数字表法,将大鼠随机分为5组(n =20)∶对照组(C组)、异丙酚25 mg/kg组(P1组)、异丙酚50 mg/kg组(P2组)、异丙酚100 mg/kg组(P3组)和异丙酚200 mg/kg组(P4组).P1组和P2组分别腹腔注射异丙酚25和50 mg/kg；P3组和P4组首次注射异丙酚50 mg/kg,翻正反射恢复时,再追加异丙酚50 mg/kg,直至给完总量.每组取5只大鼠,于苏醒后即刻抽取动脉血样进行血气分析.苏醒后放回笼内继续饲养直至9周龄,采用Morris水迷宫实验测定认知功能,处死后,取海马组织,分别采用Western blot法和RT-PCR法测定神经生长因子(NGF)和Caspase-9蛋白及其mRNA的表达；电镜下观察海马神经元超微结构.结果 5组大鼠血气分析指标差异无统计学意义(P＞0.05).与C组比较,P1组逃避潜伏期和穿越原平台次数差异无统计学意义(P＞0.05),P2组～P4组逃避潜伏期延长,穿越原平台次数减少,P1组～P4组海马NGF蛋白及其mRNA表达下调,Caspase-9蛋白及其mRNA表达上调(P＜0.05)；P1组～P4组逃避潜伏期逐渐延长,NGF蛋白及其mRNA表达逐渐下调,Caspase-9蛋白及其mRNA表达逐渐上调,P2组～P4组穿越原平台次数少于P1组(P＜0.05),但P2组～P4组间差异无统计学意义(P＞0.05)；P2组～P4组海马神经元出现核固缩、染色质边集、核碎裂、凋亡小体.结论异丙酚麻醉可损害新生大鼠的远期认知功能,且该作用与剂量有关；其机制可能与抑制NGF表达,增强Caspase-9活性有关.
목적 탐토불동제량이병분마취대신생대서원기인지공능적영향.방법 웅성SD대서100지,출생후7d,체중9～18g,채용수궤수자표법,장대서수궤분위5조(n =20)∶대조조(C조)、이병분25 mg/kg조(P1조)、이병분50 mg/kg조(P2조)、이병분100 mg/kg조(P3조)화이병분200 mg/kg조(P4조).P1조화P2조분별복강주사이병분25화50 mg/kg；P3조화P4조수차주사이병분50 mg/kg,번정반사회복시,재추가이병분50 mg/kg,직지급완총량.매조취5지대서,우소성후즉각추취동맥혈양진행혈기분석.소성후방회롱내계속사양직지9주령,채용Morris수미궁실험측정인지공능,처사후,취해마조직,분별채용Western blot법화RT-PCR법측정신경생장인자(NGF)화Caspase-9단백급기mRNA적표체；전경하관찰해마신경원초미결구.결과 5조대서혈기분석지표차이무통계학의의(P＞0.05).여C조비교,P1조도피잠복기화천월원평태차수차이무통계학의의(P＞0.05),P2조～P4조도피잠복기연장,천월원평태차수감소,P1조～P4조해마NGF단백급기mRNA표체하조,Caspase-9단백급기mRNA표체상조(P＜0.05)；P1조～P4조도피잠복기축점연장,NGF단백급기mRNA표체축점하조,Caspase-9단백급기mRNA표체축점상조,P2조～P4조천월원평태차수소우P1조(P＜0.05),단P2조～P4조간차이무통계학의의(P＞0.05)；P2조～P4조해마신경원출현핵고축、염색질변집、핵쇄렬、조망소체.결론 이병분마취가손해신생대서적원기인지공능,차해작용여제량유관；기궤제가능여억제NGF표체,증강Caspase-9활성유관.
Objective To investigate the effects of different doses of propofol anesthesia on the long-term cognitive function in neonatal rats.Methods One hundred 7-day-old male Sprague-Dawley rats,weighing 9-18 g,were randomly divided into 5 groups (n =20 each) ∶ control group (C group) and propofol 25,50,100 and 200mg/kg groups (groups P1-4,respectively).Groups P1 and P2 received intraperitoneal propofol 25 and 50 mg/kg,respectively.Groups P3 and P4 received intraperitoneal propofol 100 and 200 mg/kg,respectively,and after righting reflex completely recovered,an increment of propofol 50 mg/kg was given until the total amount was finished.Five animals in each were chosen and arterial blood samples were obtained immediately after the animals were fully awake for blood gas analysis.The rats were then continuously fed.When the rats were 9 weeks old,the spatial learning and memory function was tested by Morris water maze.The animals were then sacrificed and their brains were removed for detection of the expression of nerve growth factor (NGF) and Caspase-9 protein and mRNA in hippocampal tissues (by Western blot analysis and RT-PCR) and for microscopic examination of the ultrastructure of hippocampal neurons.Results There was no significant difference in blood gas analysis index between the 5 groups (P ＞ 0.05).Compared with group C,no significant change was found in the escape latency and frequency of crossing the original platform in group P1,the escape latency was prolonged and the frequency of crossing the original platform was decreased in groups P2-4,the expression of NGF protein and mRNA was down-regulated and the expression of Caspase-9 protein and mRNA was up-regulated in groups P1-4 (P ＜ 0.05).The escape latency was gradually prolonged,the expression of NGF protein and mRNA was gradually down-regulated and the expression of Caspase-9 protein and mRNA was gradually up-regulated in groups P1-4.The frequency of crossing the original platform was decreased in groups P2-4 compared with group P1 (P ＜ 0.05).There was no significant difference in the frequency of crossing the original platform between groups P2-4 (P ＞ 0.05).Nucleus condensation,chromatin condensation,nuclear fragmentation and apoptotic bodies were observed in groups P2-4.Conclusion Propofol anesthesia can impair the long-term cognitive function in neonatal rats,the effect is related to the dose,and inhibition of NGF expression and increase in the activity of Caspase-9 may be involved in the mechanism.