运动训练对新生期惊厥大鼠学习能力和海马ZnT1表达的远期影响

Long-term Effects of Physical Exercise on Learning Ability and ZnT1 Expression in Hippocampus of Rats with Neonatal Seizures

目的:探讨新生期大鼠单次长程或反复惊厥对学习能力和海马锌离子转运体1(ZnT1)表达的远期影响及运动训练的干预作用。方法:生后6 d(用P6表示)的SD大鼠随机分成3组各12只。单次惊厥组(SS组)和反复惊厥组(RS组)在P6吸入三氟乙醚诱导惊厥发作,持续30 min,SS组诱导P1,RS组连续P6;对照组同样操作但不吸入三氟乙醚。3组大鼠分别于P27～31、P58～61、P80～82进行3次Morris水迷宫测试,检测学习和记忆功能;同时在P51～56对SS组和RS组进行踏转轮训练,30 min,每天1次,连续P6。P82时行脑组织切片观察ZnT1在海马的表达。结果:①逃避潜伏期:各组各次逃避潜伏期均有逐渐缩短趋势,其中第1次水迷宫测试RS组P1～4潜伏期明显高于对照组(P<0.05),第5次各组差异不明显;第2次水迷宫RS组P1～2潜伏期较对照组仍显著延长(P<0.05),P3差异无显著性意义;第3次测试各组间差异不明显。②ZnT1原位杂交:RS组ZnT1 mRNA在海马表达明显高于对照组和SS组(P<0.01)。结论:新生期反复长程惊厥能够对学习功能产生远期损害;而单次长程惊厥对学习能力无明显影响。早期运动训练能够改善反复惊厥所致的学习能力损害,这可能与海马ZnT1表达上调有关。

Objective： To explore the long-term effects of neonatal seizures and physical exercise on learning ability and the expression of zinc transporter 1 （ZnT1） in hippocampus. Methods： The authors assigned twelve neonatal rats for each group： the single-seizure group （SS）, the recurrent-seizure group （RS） and the control group. The volatile agent flurothyl was used to induce 30 min seizure attack. At postnatal day 6 （P6）, the single seizures were induced only once, and recurrent seizures induced once per day for consecutive 6 days. Control rats were placed into the container for an equal amount of time to their counterpart without exposure to flurothyl. At P27-P31, P58-P61, and PS0-P82, Morris water-maze test was performed to evaluate spatial learning capacity. During P51-P56, the RS and SS groups were submitted to an aerobic exercise program 30 min per day for consecutive 6 days. The control group was maintained in the treadmill for the same time as the training group without being submitted to physical exercise. In situ hybridization method was used to detect the expression of ZnT1 mRNA in hippocampus. Results： （1） Kscape latency： In the first two Morris water-maze tests, there was a decreasing trend of escape latency in three groups, and the escape latency in RS group was significantly longer than that in control group. After physical exercise, in the last Morris water-maze tests, there was no significant difference in escape latency among three groups. （2） In situ hybridization revealed that the expression level of ZnT1 mRNA at CA3 was significantly higher in RS group than in SS and control groups （P〈0.05）. Conclusion： Recurrent but not single prolonged seizures might cause long-term effects on learning ability. Physical exercise could improve the learning capacity of RS group, which may be associated with the up-regulated expression of ZnT1 mRNA in hippocampus.