七氟烷、异氟烷对幼鼠脑细胞凋亡和远期学习记忆功能的影响

Effects of sevoflurane and isoflurane on neuroapoptosis and the long-term learning ability in newborn rat brain

目的:观察幼鼠暴露于七氟烷、异氟烷不同时间对脑细胞凋亡及远期学习记忆能力的影响。方法:出生后7d Wistar幼鼠90只随机分为5组:模拟麻醉(A组),3.6%七氟烷麻醉2h(B组),3.6%七氟烷麻醉6h(C组),2.3%异氟烷麻醉2h(D组),2.3%异氟烷麻醉6h(E组),每组幼鼠麻醉中均无缺氧及CO2蓄积发生。麻醉结束6h后采用4%多聚甲醛灌注取脑,免疫组化检测caspase-3蛋白表达;余幼鼠分别在成长至5、14周时,行Morris水迷宫实验后检测脑caspase-3蛋白表达(n=6)。结果:与A组相比,B、C、D及E组海马齿状回及CA3区caspase-3阳性细胞数明显增加,且C组多于B组,E组多于D组(P<0.05)。各组大鼠5、14周定位航行实验每日到达平台所需游泳距离无统计学差异,游泳速度、第一次穿越原平台位置时间、原平台所在象限游泳时间无统计学差异(P>0.05),但B、C、D及E组大鼠穿越原平台所在位置次数明显高于A组(P<0.05)。结论:发育期幼鼠暴露于3.6%七氟烷和2.3%异氟烷均能诱发海马神经元细胞凋亡,等效浓度异氟烷影响超过七氟烷;两药均一过性影响大鼠对不良刺激的记忆能力,但未造成大鼠远期空间记忆能力下降。

AIM： To investigate the changes of neuroapoptosis in brain and learning ability after neonatal mice exposed to inhaled sevoflurane or isoflurane.METHODS： Ninety postnatal day（P）7 Wistar rats were randomly divided into 5 groups ： group A sham anesthesia,group B 3.6% sevoflurane for 2 h,group C 3.6% sevoflurane for 6 h,group D 2.3% isoflurane for 2 h and group E 2.3% isoflurane for 6 h.Animals from each group were perfused transcardially with 0.1 mol phosphate buffer containing 4% paraformaldehyde 6 h after the end of anesthesia,and then the brains were exposed for immunohisochemistry,caspase-3 positive cells were detected.Behavioral studies with Morris water maze test were performed separately when the rats were 5-week-old and 14-week-old.RESULTS：The amounts of caspase-3 positive cells in the rats brain of Group B,C,D and E were greater than that in Group A,and the amount in group C was greater than that in gourp B,in group E more than that in group B（P〈0.05）.When face the spatial reference memory task or space exploration task,rats from different groups make it uniformly.Anesthetic rats and control rats performed similarly in terms of path length when learning to swim to the platform during locating trials.No rats showed significantly higher levels of retention during the probe trials in terms of target quadrant time,platform crossings and platform location time（P〈0.05）,but the number of platform crossings in group B,C,D and E was significantly higher than that in gourp A（P〈0.05）. CONCLUSION： Exposure to the concentration of 3.6% sevoflurane or 2.3% isoflurane could cause brain cell apoptosis of newborn rats.Isoflurane could cause more insults to brain than sevoflurane at an equivalent concentration.The memory ability to pessimal stimulation is decreased as the anesthesia mice 5 weeks old,such changes recede along with the growth of rats.Exposure to sevoflurane and isoflurane does not affect the spatial reference memory of newborn rat during their growth.