异丙酚或依托咪酯对幼龄大鼠海马神经元凋亡的影响

Effects of propofol and etomidate on apoptosis in hippocampal neurons in rats

目的评价异丙酚或依托咪酯对幼龄大鼠海马神经元凋亡的影响。方法雄性sD大鼠140只，4周龄，体重40—60g，采用随机数字表法，将大鼠随机分为7组（n=20）：对照组（C组）、异丙酚50mg／kg组（PJ组）、异丙酚100mg／ks组（P2组）、异丙酚200mg／kg组（P3组）、依托咪酯10mg／kg组（E1组）、依托咪酯30mg／kg组（E2组）和依托咪酯60mg／kg组（E，组）。P1组和E1组单次腹腔注射异丙酚50mg／ks或依托咪酯10mg／kg；P2组、P3组、E2组和E3组首次注射异丙酚50mg／kg或依托咪酯10mg／kg，待大鼠有体动反应后，再每次追加异丙酚50mg／kg或依托咪酯10mg／kg，直至给完总量。大鼠苏醒2h时，每组取5只大鼠，抽取动脉血样进行血气分析。每组取5只大鼠，取海马CA1区，电镜下观察超微结构。每组取5只大鼠，取海马组织，采用RT-PCR法测定SurvivinmRNA和Caspase-3 mRNA的表达。每组取5只大鼠，取海马组织，采用Westernblot法测定Survivin蛋白和Caspase-3蛋白的表达。结果七组间pH值、PaO2、PaCO2、HCO3-、BE和Sa02比较差异无统计学意义（P〉0．05）。与c组比较，P1组、P2组、E1组和E2组海马Survivin和Caspase-3的mRNA和蛋白表达差异无统计学意义（P〉0．05），P3组和E3组海马SurvivinmRNA和蛋白表达下调，Caspase．3mRNA和蛋白表达上调（P〈0．05），海马CA1区神经元出现核固缩、染色质边集及凋亡小体。结论较大剂量异丙酚和依托咪酯可能通过抑制Survivin的表达，增强Caspase-3的活性，导致幼龄大鼠海马神经元凋亡。

Objective To investigate the effects of propofol and etomidate on apoptosis in hippocampal neurons in rats. Methods One hundred and forty male 4 weeks old SD rats were randomly divided into 7 groups （n = 20 each）： control group （group C）; groups P1.2.3 received intraperitoneal （IP） propofol 50, 100 and 200 mg/kg and groups Ei.2.3 received IP etomidate 10, 30 and 60 mg/kg respectively. Arterial blood samples were obtained at 2 h after the animals were fully awake for blood gas analysis. The animals were then sacrificed and their brains removed for microscopic examination of the ultrastructure of neurons in hippocampal CA1 area and detection of Survivin and Caspase-3 mRNA and protein expression in hippocampus by RT-PCR and Western blot analysis. Results There was no significant difference in PaO2, PaCO2, SaO2, HCO3- , BE and pH value among the 7 groups. The neurons in CA1 area were basically normal in groups C, P1 and E1 while condensation of the chrematin of the nucleus and apoptotic bodies were observed in groups P3 and E3 . Caspase-3 mRNA and protein expression was significantly up-regulated while Survivin mRNA and protein down-regulated in groups P3 and E3 . Conclusion High dose of propofol and etomidate may induce apoptosis in hippocampal neurons in rats by up-regulation of Caspase-3 expression and down-regulation of Survivin expression.