孕期癫痫发作对子代大鼠海马结构和认知功能的影响  

Effects of prenatal maternal seizure on hippocampal damage and cognitive deficits in offspring rats

作　　者：卢艳[1] 王维平[2] 王秀霞[1] 冯娇娇[1] 郭卓平[1] 刘良敏[2] 谢涛[2] 赵冉冉[2] 蔡云雷[2] 

机构地区：[1]河北医科大学第二医院儿科,石家庄050000 [2]河北医科大学第二医院神经内科,石家庄050000

出　　处：《中华儿科杂志》2016年第10期746-751,共6页Chinese Journal of Pediatrics

基　　金：河北省人口计生委科研课题（2013-A25）

摘　　要：目的 探讨孕鼠电点燃癫痫发作对子代海马结构的损伤及仔鼠成年后认知功能的影响和机制.方法 成年雌性SD大鼠按随机数字表随机分为3组：正常对照组（8只）、电点燃组（12只）和假手术组（8只）.首先制备杏仁核慢性电点燃癫痫孕鼠模型,孕期给予每2日1次电刺激.孕鼠自然分娩后比较各组仔鼠数目、存活率及出生体重有无差异;通过孕鼠胎盘HE染色观察其病理改变;通过海马组织尼氏染色观察子代近远期神经损伤情况;通过Morris水迷宫观察子代远期学习记忆能力.采用方差分析和x2检验进行组间统计学比较.结果 电点燃组新生大鼠存活率明显低于假手术组和正常对照组[81％（66/82）比95％ （78/82）和95％（82/86）,x2=13.817,P=0.001];而在每只孕鼠产仔数量和仔鼠出生体重方面,电点燃组与假手术组和正常对照组分别比较,差异均无统计学意义（F =0.312、0.257,P=0.736、0.776）.孕鼠胎盘组织HE染色显示,电点燃组绒毛和迷路带结构较正常对照组和假手术组明显异常.子代海马组织病理显示,电点燃组近、远期子代海马尼氏染色均显示神经元丢失,而新生子代更为显著.成年子代Morris水迷宫检测显示,在定位航行实验的第3、4、5天,电点燃组逃避潜伏期均明显长于假手术组和正常对照组[（36±8）比（29±8）和（25±6）、（29±8）比（19±9）和（17±5）、（30±11）比（10±4）和（14±4）s,F=6.276、7.518、18.422,P=0.030、0.003、0.000];而空间探索试验中,电点燃组穿越平台区域次数明显少于假手术组和正常对照组[（4.4±1.7）比（7.2±1.6）和（8.5±1.3）次,F=18.377,P=0.000],同时在平台象限游泳时间方面也明显短[（27 ±8）比（58±11）和（68±13）s,F=35.993,P=0.000].在水迷宫实验各项结果中,假手术组与正常对照组之间差异均无统计学意义（P均＞0.05）.结论 孕期癫痫发作可导致子代近期和远期的海�Objective To observe hippocampal damage and cognitive impairment of offspring exposed to prenatal maternal seizure induced by amygdala kindling,and to explore the underlying mechanism by the detection of pathological changes of placenta.Method Adult fcmale SD rats were randomly divided into three groups：control group （8 rats）,kindling group （12 rats） and sham group （8 rats）.All the rats were allowed to mate after one week＇s fully kindling.The pregnant rats in kindling group received electric stimulation every 48 h.Dams were allowed to deliver naturally.Effects of maternal seizure on the number of offspring,the survival rate and body weight of pups were observed.HE staining was used to visualize histopathological changes of placenta.Morris water maze test was used to assess the cognitive function and Nissal＇s staining to detect hippocampal morphology of the offspring.One-way ANOVA analysis and x2 test were used.Result Compared with the sham group （95% （78/82）） and the control group （95% （82/86））,the survival rate of pups in kindling group （81% （66/82））was much lower （x2 =13.817,P =0.001）.There were no significant differences in the number of pups per litter and pups birth-weight between kindling group and sham group or control group（F=0.312 and 0.257,P =0.736 and 0.776）.HE staining showed that placental tissues from control and sham groups were normal whereas the histologic abnormalities of placentas from kindling group were characterized by thickening of the villus vascular walls,luminal stenosis,trophoblasts hyperplasia,abnormalities of trophoblasts with nuclear pyknosis and karyorrhexis and accumulation of inflammatory lymphocytes in labyrinthine zone.Nissl staining showed that neurons in hippocampus of P0 （0 d after birth） and P84 （84 d after birth） offspring from control and sham groups were normal,but neuronal damages were obvious in hippocampus of P0 and Ps4 offspring from kindling groups,and the damages in P0 pups were severe with a marked loss of n

关 键 词：癫痫 妊娠 认知 海马 子代 

分 类 号：R742.1[医药卫生—神经病学与精神病学]