跑台运动预干预对睡眠剥夺大鼠行为学改变、前额叶皮质氧化应激及c-fos表达的影响

Effects of Treadmill Exercise Pre-intervention on Behavior Changes,Oxidative Stress Damage and c-fos Expression within Prefrontal Cortex in Sleep Deprived Rats

目的观察4周中等强度跑台运动预干预对睡眠剥夺大鼠焦虑样行为及空间学习记忆能力、血清皮质酮含量和前额叶皮质(prefrontal cortex,PFC)氧化应激水平及c-fos表达的影响。方法将40只大鼠随机分为4组,即正常对照组、运动组、睡眠剥夺组(sleep deprivation,SD)及睡眠剥夺运动组(SD+E)。除正常对照组及睡眠剥夺组大鼠,运动组大鼠进行4周跑台运动预干预,运动结束后睡眠剥夺组及睡眠剥夺运动组大鼠睡眠剥夺建立大鼠72h SD模型(小平台水环境法),然后运用开场实验及明暗箱探索实验评估所有大鼠焦虑样行为,八臂迷宫实验测试大鼠空间学习记忆能力;行为学测试结束后检测所有大鼠血清皮质酮及前额叶皮质自由基水平,用免疫组织化学结合图像半定量方法计算前额叶皮质c-fos神经元的分布。结果 (1)与正常对照组比较,开场实验(open field test,OFT)测试中,SD组大鼠穿越格数(crossing numbers)、直立次数(rearing numbers)及中央格停留时间百分比均显著减少,粪便颗粒增多;明暗箱探索实验中(Light-dark,LD),SD组大鼠明箱停留时间及穿越次数均显著减少;八臂迷宫实验(eight arm maze tests,ERM)中SD组大鼠学习记忆能力下降,血清皮质酮水平显著增高,前额叶皮质SOD及GSH-px活性显著下降,MDA含量增加,c-fos表达显著增强。(2)与SD组大鼠比较,OFT测试中,SD+E组大鼠穿越格数、直立次数及中央格停留时间百分比均显著增加,粪便颗粒减少;LD探索实验中,SD+E组大鼠明箱停留时间显著延长,ERM实验中大鼠学习记忆能力显著改善;SD+E组大鼠血清皮质酮水平显著下降,前额叶皮质SOD活性显著上调,GSHpx活性无显著性差异,MDA含量下降,c-fos表达显著下降。结论结果显示,跑台运动预干预可以减弱睡眠剥夺对学习记忆的影响、改善睡眠剥夺大鼠焦虑样行为,可能与跑台运动改善HPA轴功能失调、增强前额叶皮质抗氧化能力及下调前额叶皮质c-fos的过度表达有关。

Objetive To explore the effects of the prior 4-week treadmill exereise on the anxiety-like behavior and learning and memory, the blood serum cort level, oxidative stress level and c-los expression within prefrontal cortex（PFC） in the sleep-deprived （SD） rats. Methods 40 rats were randomly divided into 4 groups ： the normal control group （NC） , the exercise group （EC）, sleep deprived group （SD） and exercised ＋ sleep deprived group （SD ＋ E）. EC group and SD ＋ E group rats were exposed to 4 weeks of regular treadmill exercise, then the SI） and SD ＋ E group rats were sleep deprived for 72h using the small platform over water method. To assess the anxiety like behavior and learning and memory after SD, all animals underwent behavioral experiment（ OFT, LD and ERM tests）. Subsequently, the blood serum eortisol and PFC free radieal level were examined following behavior test and e-los expression within PFC was immunohistochemically stained by the ABC method and counted the number of c-fos. Results 1 ） Compared with the NC group, crossing squares, rearing numbers and the percent of the staying central cell time significantly decreased and feces particles increased in the OFT; light box time and crossing numbers decreased in LD test and learning and memory was impaired in ERM test; the level of serum cortisol increased, SOD and GSH-px activities reduced, MDA concentration increased and c-fos expression enhanced within PFC in SD group rats ; 2） Compared with the SD group, crossing squares, rearing numbers and the percent of the staying central ceil time significantly increased, teces particles decreased in OFT; light box time prolonged in LD test and learning and memory was enhanced in SD ＋ E group rats ; the cort level significantly decreased, SOD activity significantly increased, GSH-px activity was not significant difference, MDA concentration decreased and c-los expression reduced in rat PFC of SD ＋ E group rats. Conclusion Treadmill exercise can attenuate the deleterious effects of sleep deprivation on learning and memory and improve sleep deprivation induced anxiety-like behavior, its possible mechanism might be that treadmill exercise ameliorate the dysregulation of HPA axisagonism, reinforce PFC antioxidant capbility and decreased c-fos expression in PFC at the same time.