【摘要】 目的研究同等剂量的异氟醚和七氟醚对新生大鼠额叶皮质神经细胞凋亡的影响以及其与Akt/GSK3β通路的关系。方法 5窝出生后第7天(P7)的新生大鼠,每窝取12只,共60只,随机均分为异氟醚组(I组),七氟醚组(S组)和对照组(C组)。各组分别吸入0.5 MAC的异氟醚(1.1%)、七氟醚(1.8%)和空气4 h,在麻醉结束后2 h每窝每组各取1只幼鼠制备脑组织切片,免疫组织化学法检测额叶皮质区caspase-3表达;另外,C组在麻醉处理0 h,I组和S组分别在麻醉2,4 h取新鲜脑皮质,Western Blot检测磷酸化Akt(p-Akt)、Akt及GSK3β表达的变化。结果 I组和S组caspase-3表达分别较对照组增加659.38%(P<0.001)和191.25%(P<0.001),I组比S组增加160.73%(P<0.01);I组p-Akt表达在麻醉2和4 h较对照组降低66.31%(P<0.01)和36.06%(P<0.01),S组在2 h较对照组降低66.31%(P<0.01),4 h与对照组无统计学差异;I组GSK3β表达在麻醉2和4 h均较对照组显著增加82.48%(P<0.01)和79.52%(P<0.01),S组在2和4 h均较对照组显著增加40.73%(P<0.05),4 h与对照组无统计学差异。结论 0.5 MAC异氟醚比七氟醚诱导更多新生大鼠大脑额叶皮质神经细胞caspase-3表达或凋亡,可能与异氟醚更加显著地抑制p-Akt及增加GSK3β表达有关。更多还原

【Abstract】 OBJECTIVE To investigate the effects of isoflurane and sevoflurane at the same dose on apoptosis of the frontal cortex neuron in neonatal rats and the role of Akt/GSK3β pathway.METHODS Twelve neonatal rats on postnatal day 7 in each litter(altogether 5 litters,60 neonatal rats in total)were randomly and evenly assigned to control group(C group),isoflurane group(I group)and sevoflurane group(S group).The rats in I group,S group or C group were respectively exposed to 0.5 MAC isoflurane(1.1%),sevoflurane(1.8%)and air for 4 h.The brain of neonatal rats were perfused and embedded by paraffin.Caspase-3 expression in the frontal cortex of brain were detected by immunohistochemistry staing.Besides,the fresh cortex were separated at 0 h in C group and at 2,4 h in I group and S group,phospho-Akt,Akt,GSK3β expression were detected by Western blot staining.RESULTS Caspase-3 positive cells in the frontal cortex increased by 659.38%(P<0.001)in I group and 191.25%(P<0.001)in S group when compared with C group,and increased by 160.73%(P<0.01)in I group when compared with S group.The phospho-Akt protein in the cortex decreased by 66.31%(t=6.23,P<0.01)at 2 h and 36.06%(t=6.22,P<0.01)at 4 h in I group,and decreased by 66.31%(t=6.84,P<0.01)at 2 h while there were no significant difference at 4 h in S group when compared with C group.The GSK3β protein in the cortex increased by 82.48%(P<0.01)at 2 h and 79.52%(P<0.01)at 4 h in I group,while increased by 40.73%(P<0.05)at 2 h and no significant difference at 4 h in S group when compared with C group.CONCLUSION Isoflurane at 0.5 MAC induced more apoptosis in the frontal cortex neuron of the neonatal rats on postnatal day 7 than sevoflurane at same dose.The mechanism may be that isoflurane decreases the expression of phosphor-Akt and increases the expression of GSK3β more than sevoflurane.更多还原