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目的探讨新生期大鼠单次长程或反复惊厥对学习、记忆能力和海马突触后致密物质CaMKⅡ表达的影响及运动训练的干预作用。方法生后6d的SD大鼠36只随机分成单次长程惊厥组(SS组)、反复惊厥组(RS组)和对照组,每组12只。3组大鼠分别于生后27～31d、58～61d、80～82d进行3次Morris水迷宫实验。期间于生后51～56d对SS组和RS组进行踏转轮训练。最后制作脑组织切片观察CaMKⅡ在海马中的表达。结果①搜寻策略:第1次Morris水迷宫实验各组1～5d边缘式搜寻比例均呈逐渐减少趋势,但RS组第3天～第4天边缘式搜寻比例仍明显高于对照组,差异具有统计学意义(P<0.01),同时趋向式搜寻比例则均呈逐渐增加趋势,但RS组第3天～第4天趋向式搜寻比例仍明显低于对照组,差异具有统计学意义(P<0.01);而第2次和第3次水迷宫实验3组间趋向式和直线式搜寻策略差异无统计学意义。②记忆实验:RS组1～3d趋向式搜寻比例均明显低于对照组,差异具有统计学意义(P<0.05)。③CaMKⅡ原位杂交:各组CaMKⅡmRNA在海马均有明显表达,但是在齿状回RS组表达明显低于对照组,差异具有统计学意义(P<0.01)。结论新生期反复长程惊厥能对学习和记忆功能产生远期损害,可能与海马记忆分子CaMKⅡ表达下调有关;而单次长程惊厥对学习记忆无明显影响。早期运动训练能明显改善反复惊厥所致的学习能力损害,但对记忆能力效果仍较差。
Objective To investigate the effects of single long-term or recurrent seizures on learning and memory abilities and hippocampal postsynaptic density (CaMKⅡ) expression in hippocampus and the effect of exercise training. Methods Sixty-six SD rats were randomly divided into single long-term convulsion group (SS group), recurrent seizure group (RS group) and control group, with 12 rats in each group. The rats of three groups were subjected to Morris water maze test three times at 27-31 days, 58-61 days and 80-82 days after birth respectively. 51 to 56 days after birth on the SS group and RS group tread wheel training. Finally, brain tissue sections were made to observe the expression of CaMKII in hippocampus. Results (1) Search strategy: In the 1st Morris water maze test, the edge-to-edge search ratio decreased gradually from 1 day to 5 days in each group. However, the margin search percentage from the 3rd day to the 4th day of RS group was still significantly higher than that of the control group (P <0.01), while the proportion of trend search showed a trend of increasing gradually. However, the proportion of trend searching from the 3rd day to the 4th day of RS group was still significantly lower than that of the control group (P < 0.01). However, there was no significant difference in trend and linear search strategies among the 3 groups in the 2nd and 3rd water maze test. ② Memory test: The proportion of 1 ~ 3d trend search in RS group was significantly lower than that in control group, the difference was statistically significant (P <0.05). (3) CaMKⅡin situ hybridization: CaMKⅡmRNA in each group was obviously expressed in hippocampus, but the expression in the dentate gyrus RS group was significantly lower than that in the control group, the difference was statistically significant (P <0.01). Conclusions The long-term recurrent seizures in the neonatal period can cause long-term damage to learning and memory functions, which may be related to the down-regulation of CaMKⅡ expression in hippocampal memory cells. However, single long-range convulsions have no significant effect on learning and memory. Early exercise training can significantly improve learning ability caused by recurrent seizures damage, but the memory effect is still poor.