丰富环境对七氟醚吸入诱发新生大鼠远期认知功能障碍的影响

Effects of enriched environment on sevoflurane-induced long-term cognitive dysfunction in neonatal rats

目的观察丰富环境对七氟醚吸入诱发新生大鼠远期认知功能障碍的影响。方法 6日龄新生雄性SD大鼠30只随机均分为三组:O2+标准环境组(OS组)、七氟醚麻醉+标准环境组(SS组)和七氟醚麻醉+丰富环境组(SE组)。SS、SE组分别在日龄6、7、8d时,每天接受1次2h的3%七氟醚麻醉,氧浓度100%;O2组在相应日龄吸入100%氧气。出生后第8天起至行为学测试前分别进行标准环境和丰富环境饲养,连续4周。第35天行旷场实验。第36天行场景性、条件性恐惧实验训练。第37、38天行场景性、条件性恐惧实验测试。行为学测试结束后2h,每组各取4只大鼠海马组织,采用Western blot法检测Synapsin-1、PSD-95、c-fos及BDNF含量。结果旷场实验测试中,三组探索路程和中央格停留时间差异无统计学意义。场景性恐惧实验测试中,与SS组比较,OS、SE组僵直反应明显增加(P<0.05)。条件性恐惧实验测试中,三组僵直反应差异无统计学意义。与SS组比较,OS、SE组海马Synapsin-1、PSD-95、c-fos和BDNF含量明显增加(P<0.05)。结论七氟醚麻醉可致新生大鼠远期海马依赖性认知功能受损,丰富环境可改善此种损伤,其机制可能与增加突触可塑性相关蛋白表达有关。

Objective To observe the effects of enriched environment on sevoflurane-induced long-term cognitive dysfunction in neonatal rats. Methods Thirty male Sprague Dawley rats at postnatal day 6 were randomly divided into the following three groups （n= 10）： 02 ＋ standard environ ment group （group OS）, sevoflurane anesthesia ＋ standard environment group （group SS） and sevoflurane anesthesia＋enriched environment group （group SE）. Animals were subjected to 100% 02 or 3% sevoflurane plus 100% 02 2 h daily for 3 consecutive days, respectively. Thereafter, animals in different groups were raised in a standard environment or enriched environment for 4 weeks, respectively. Open field was performed at postnatal day 35, the training fear conditioning test was performed at postnatal day 36, and the contextual and the cued fear conditioning tests were performed at postnatal day 37 and 38, respectively. The hippocampus was harvested 2 h after the behavioral test for the determination of the content of Synapsin-1, PSD-95, c-fos and BDNF （n=4）. Results In the open field test, there was no significant difference in the total travel distance and the time spent in the center of the arena among the three groups. In the contextual fear conditioning test, the freezing time in group OS and group SE was significantly longer compared with group SS （P〈0. 05）. However, in the cued fear conditioning test, no difference was observed in the freezing time among the three groups. Compared with group SS, the content of Synapsin-1, PSD-95, c-los and BDNF in group OS and group SE was significantly increased（P〈0.05）. Conclusion Neonatal rats exposed to sevoflurane anesthesia presented hippocampus-dependent long-term cognitive dysfunction. However, enriched environment can alleviate this impairment, which was associated with the up-regulation of synaptic plasticity related proteins in hippocampus.