运动训练对发育期大鼠反复惊厥所致认知损害的干预及机制研究

关键词：惊厥  运动训练  学习记忆  海马  谷氨酸受体2

Keywords:convulsion  physical exercises  learning and memory  Glutamic acid receptor 2

摘要：

      摘要 目的：探讨发育期大鼠青霉素点燃致反复惊厥发作对学习记忆能力远期影响及踏转轮运动训练的干预效果及机制。 方法：56只21日龄（PD21，下同）健康雄性SD大鼠随机分为单纯对照组（CONT1）10只，对照加运动训练组（CONT2）10只，单纯惊厥组（EXP1）及惊厥加运动训练组（EXP2），其中后两组共36只，均采用腹腔注射（ip）青霉素（4.5×106U·kg-1·d-1）连续6天，以制备惊厥模型。两组对照组同时给予同等剂量的生理盐水腹腔注射。将制备成功的20只惊厥模型进行随机分组，其中EXP1组10只，EXP2组10只。四组SD大鼠分别于PD39-PD43、PD61-PD64进行两次Morris水迷宫测试以检测各组大鼠的学习、记忆能力，其间于PD49-PD54对CONT2组和EXP2组进行踏转轮运动训练；免疫组织化学染色观察海马各区谷氨酸受体2（GluR-2）表达情况。 结果：①第一次水迷宫测试，四组间逃避潜伏期存在显著性差异（F=5.56, P＜0.01），且两惊厥组潜伏期均明显长于两对照组（P＜0.05）；空间搜索实验中，两惊厥组穿越原平台所在位置的次数明显少于两对照组（P＜0.05）；②第二次水迷宫测试，经过运动训练的EXP2组的潜伏期明显短于EXP1组（q=4.37, P＜0.05）；两惊厥组穿越原平台所在位置的次数仍明显少于两对照组（P＜0.05），且EXP1 组与EXP2组间无明显差异（P＞0.05）；③两惊厥组海马齿状回及CA3区GluR2阳性表达率均明显低于两对照组（P＜0.05）。 结论：发育期青霉素诱发反复长程惊厥能够对学习和记忆功能产生远期的损害，可能与海马GluR2表达下调有关。运动训练能够明显改善反复惊厥所致的学习能力损害，而对记忆能力效果较差，可能与海马GluR2表达上调有关。

Abstract:

      Abstract Objective：To explore the long-term effects of physical exercises on penicillin induced recurrent convulsion with learning and memory deficits in developing rats and its mechanism. Method：Fifty-six male SD rats (postnatal days [PD] 21) were randomly divided into four groups: control group(CONT1), control plus exercises group(CONT2), convulsion group(EXP1) and convulsion plus exercises group(EXP2). Twenty rats were assigned for two control groups, each n=10; the surplus 36 rats were kindled by penicillin once per d, consecutive 6d for creating convulsion models. Control rats were injected equal amount of normal sodium(NS) into abdominal cavity at the same time. The 20 qualified models of convulsion rats were randomly divided into two EXP groups. On PD39-PD43 and PD61-PD64, subjects of the four groups were tested with Morris water maze, and from PD49 to PD54, the rats of CONT2 and EXP2 were given exercises of running wheels, twice a d for consecutive 6d. The expression of glutamicacid receptor 2(GluR2) in hippocampus was detected. Result: ①In the first Morris water maze test, there were significant differences of latency among four groups (F=5.56, P＜0.01), and the latency of two EXP groups were significantly longer than two CONT groups (P＜0.05); In the probe trial, the frequency of two EXP groups passing through target area were significantly less than that of two CONT groups. ②In the second water maze test, there were significant effects of exercises on the latency of EXP2 group comparing to EXP1 group(P＜0.05); the frequency of two EXP groups passing through target area were still significantly less than that of two CONT groups after exercises training(P＜0.05),and there was no significant difference between EXP1 and EXP2 groups. ③In the immunohistochemical staining of GluR2, the gray values in hipocampus of two convulsion groups were significantly lower than that of two control groups(P＜0.05). Conclusion: Penicillin induced recurrent convulsion could cause long-term effects on learning and memory in rats, which may be associated with down-regulated GluR2 expression in hippocampus. Physical exercises could improve learning capacity, of convulsion rats but not memory capacity.