中文摘要：

在建立发育期大鼠青霉素点燃模型的基础上，探讨点燃后至成年期不同发育阶段空间学习记忆能力改变，以及对海马记忆分子钙／钙调蛋白依赖的蛋白激酶Ⅱα（CaMKⅡα）、突触可塑性相关基因3（PRG-3）、抗惊厥脑肠肽胆囊收缩素（CCK）、锌离子转运体1（ZnT-1）和3（ZnT-3）表达的远期影响．生后29天（P29）的SD大鼠随机分为青霉素点燃模型组（RS组，n=39）及生理盐水对照组（NS组，n=21）．RS组隔曰腹腔注射青霉素，按体重5．60×10^6U／kg，连续6次，NS组以同样方法腹腔注射生理盐水．于末次惊厥后1．5、3、6和12h透射电镜观察海马凋亡及自噬，于末次惊厥后1h进行脑电记录，于末次惊厥后24h原位末端标记凋亡法（TUNNEL）检测海马凋亡细胞．分别于P51～P56、P81～P84、P92～P95进行3次Morris水迷宫实验，检测大鼠的学习记忆能力．最后，采用Timm染色观察海马苔藓纤维发芽，实时定量RT—PCR测定海马CaMKⅡα、PRG-3、CCK、ZnT-1和ZnT-3的表达．结果如下：a．电镜显示末次惊厥后1．5～12h可见大鼠海马本部神经元内溶酶体被激活，自噬小体形成，12h自噬和凋亡同时存在；TUNNEL显示凋亡细胞明显增多护〈0．05）．b．RS组末次惊厥后3～5rain脑电图记录显示额叶丛集放电，棘波和尖波阵发．c．Morris水迷宫实验显示，第1次测试各组逃避潜伏期均呈逐渐下降趋势，但RS组第5天潜伏期明显高于NS组，具有显著性差异（P〈0．05），RS组第2次水迷宫测试中第1天潜伏期明显高于NS组，具有统计学意义，第3次水迷宫第2天的潜伏期仍明显高于NS组，具有统计学意义．d．在Morris水迷宫搜寻策略分析中采用秩和检验，第1次水迷宫对照组在第4天和第5天成绩明显优于RS组，具有统计学意义（P〈0．01），第2次和第3次水迷宫中对照组3天成绩均明显优于RS组，具有统计学意义（P〈0．

英文摘要：

Epilepsy in children is associated with a broad spectrum of cognitive deficits, which is associated with hippocampal mossy fiber sprouting. The underlying molecular mechanisms involved in mossy fiber sprouting in hippocampus following developmental seizures are not completely known. The timing of cognitive dysfunction and the relation of this cognitive impairment to calcium/calmodulin-dependent protein kinase Ⅱ （CaMK- Ⅱ ）, plasticity related gene 3 （PRG-3）, cholecystokinin （CCK）, zinc transporter 1 and 3 （ZnT-1 and ZnT-3） in hippocampus were studied. A seizure was induced by penicillin quaque die altema in Sprague-Dawley rats from postnatal day 29 （P29）. Rats were assigned into the recurrent seizure group （RS, seizures were induced in eleven consecutive days, n=39） and the control group （NS, n=21）. At 1.5 h, 3 h, 6 h and 12 h after the last seizure, apoptosis and autophagy were detected by transmission electronmicro-scopy （TEM） or in situ end labeling （TUNNEL）. Electro-corticogram was observed after the last seizure. During P51 to P56, P81 to P84 and P92 to P95, the rats were tested for spatial learning and memory abilities with automatic Morris water maze task. On P95, mossy fiber sprouting and gene expressions in hippocampus were determined subsequently by Timm staining and real time RT-PCR methods. The results are as follows： a. TEM revealed the formation of autophagosomes and apoptosis in hippocampus after kindling. In the hippocampal neurons of the controls, chromatin and cytoplasmic organoids showed eumorphism with nuclear membrane integrity; 1.5 h after the last penicilin-induced recurrent seizures, ＂C＂ -morphous double membrane structure of dilated endocytoplasmic reticulum could be observed; 3 h after the last seizures, autophagosome appeared with manifest dilated endocytoplasmic reticulum; 6-12 h after the last seizures, the hippocampal neurons showed apoptotic feature such as nuclear chromatinic pyknosis and verge-aggregation. TUNNEL staining also showed el