丙泊酚对新生大鼠远期神经行为学的影响及机制

Effects of Propofol on long term neuroethology of neonatal rats and its mechanism

摘要:

目的：研究丙泊酚对新生大鼠远期神经行为学的影响及机制。方法：新生7 d SD大鼠72只随机分为3组（n=24只），雌雄各半：对照组（C组）和丙泊酚单次注射组（P1组）腹腔注射生理盐水7.5 ml/kg，1次/d，连续6 d；第7天分别注射生理盐水7.5 ml/kg和丙泊酚75 mg/kg；丙泊酚多次注射组（P2组）腹腔注射丙泊酚75 mg/kg，1次/d，连续7 d。第7天注射完毕后15 min，每组随机抽取3只大鼠测定动脉血气和血糖；30、90 d和180 d 3个时间点,每个时间点各组随机抽取7只进行旷场实验和Morris水迷宫测试；取大鼠海马CA1区组织，用流式细胞仪测定神经元凋亡率并用体视学方法对锥体细胞形态学进行定量分析。结果：在30 d时，与对照组（C组）和丙泊酚单次注射组（P1组）相比，丙泊酚多次注射组（P2组）空间学习记忆功能和探究功能明显降低（P＜0.05），海马CA1区神经元凋亡率明显增高（P<0.05）；与C组相比，P1组和P2组海马CA1区锥体细胞体积密度Vv（Volume density,Vv)和表面积密度Sv（Surface area density,Sv)出现不同程度下降（P＜0.05），与P1组相比，P2组下降程度更为明显（P＜0.05）；在90d和180 d时，3组大鼠的各项指标没有明显差异。结论：丙泊酚多次注射可导致新生大鼠远期认知功能减退，可能与神经元凋亡率增加以及锥体细胞减少及形态改变有关。

Abstract:

Objective:To investigate the effects of Propofol on long term neuroethology of neonatal rats and its mechanism.Methods:Totally 72 seven-day-old neonatal rats were randomly divided into group C,group P1 and group P2 (n=24).The rats in group C and group P1 were injected intraperitoneally with 7.5 ml/kg normal saline q.d for consecutive six days and on 7th/ d,the rats in group C were injected with 7.5 ml/kg normal saline while those in group P1 were injected with 75 mg/kg Propofol.The rats in group P2 were received 75 mg/kg Propofol q.d for consecutive seven days. On 7th d,the artery blood gas and glucose were tested for three rats randomly chosen in each group at 15 min after the intraperitoneal injection .On 30th,90th and 180th,seven rats randomly chosen in each group were examed by Morris water maze and open-field test.The hippocampal CAI region was decapitated in rats,the apoptosis rates of the neurons were measured by flow cytomery and the morphologic changes of the pyramidal cells were assessed quantitatively by stereology method.Results:The learning,memorizing and exploring function on 30th were declined significantly and the neuron apoptosis rates in CAI region were increased markedly in group P2 compared with those in group C and group P1(P<0.05).The volume density (Vv) and surface area density (Sv) in hippocampal CAI region in group P1 and P2 were declined with various degrees compared with those in group C (P<0.05),with more obvious decline in group P2.On 90th and 180th/d,there was no difference in each item among three groups.Conclusion:Multiple propofol injections may impair long term neuroethology of neonatal rats,which may associated with increased neuron apoptosis and morphologic change of pyramidal cells.