拉莫三嗪对癫痫大鼠学习记忆能力及海马组织中Bax和Bcl-2蛋白表达的影响  

Effect of lamotrigine on spatial learning and memory and the expression of Bax and Bcl-2 protein in hippocampus of epileptic rats

作　　者：石景鹤[1,2] 高静[1,3] 王家勤[1] 

机构地区：[1]新乡医学院第三附属医院儿科,河南新乡453003 [2]郑州市儿童医院神经内科,河南郑州451000 [3]郑州市儿童医院内分泌科,河南郑州451000

出　　处：《新乡医学院学报》2017年第1期10-13,共4页Journal of Xinxiang Medical University

基　　金：河南省医学科技攻关计划项目(编号:201003077)

摘　　要：目的探讨拉莫三嗪对戊四氮致癫痫大鼠认知功能及海马组织中Bax、Bcl-2蛋白表达的影响。方法将健康雄性Sprague-Dawley大鼠100只随机分为正常组、模型组及拉莫三嗪低、中、高剂量组,每组20只。模型组及拉莫三嗪低、中、高剂量组大鼠每天腹腔注射戊四氮35 mg·kg^(-1)进行造模;正常组大鼠腹腔注射同体积生理盐水。造模成功后,正常组大鼠继续每日腹腔注射生理盐水;其余4组大鼠继续腹腔注射戊四氮,在此基础上,拉莫三嗪低、中、高剂量组大鼠分别给予拉莫三嗪20、30、60 mg·kg^(-1)·d^(-1)灌胃,模型组大鼠给予生理盐水,共2周。用Morris水迷宫实验评价大鼠的认知功能,免疫组织化学方法检测大鼠海马组织中Bax、Bcl-2蛋白表达。结果与正常组比较,模型组大鼠各时间点逃避潜伏期显著延长(P<0.05);拉莫三嗪低、中、高剂量组大鼠各时间点逃避潜伏期均短于模型组(P<0.05,P<0.01);拉莫三嗪低、中、高剂量组大鼠逃避潜伏期两两比较差异均有统计学意义(P<0.05)。空间探索实验结果显示,模型组大鼠记忆探索正确时间短于正常组(P<0.05);与模型组比较,拉莫三嗪低、中、高剂量组大鼠记忆探索正确时间显著增加(P<0.05);拉莫三嗪低、中、高剂量组大鼠记忆探索正确时间两两比较差异均有统计学意义(P<0.05)。与正常组比较,模型组大鼠海马组织中Bax蛋白表达增加,Bcl-2蛋白表达减少(P<0.01);拉莫三嗪低、中、高剂量组大鼠海马组织中Bax蛋白表达均低于模型组,Bcl-2蛋白表达均高于模型组(P<0.05);拉莫三嗪低、中、高剂量组之间大鼠海马组织中Bax、Bcl-2蛋白表达两两比较差异均有统计学意义(P<0.05)。结论拉莫三嗪对戊四氮致癫痫大鼠海马神经元有保护作用,并能提高大鼠的学习、记忆和判断能力。Objective To explore the effect of lamotrigine on the cognitive function and expression of Bax and Bcl-2protein in hippocampus of epileptic rats induced by pentetrazole（ PTZ）. Methods One hundred healthy male Sprague-Dawley rats were randomly divided into the normal group,model group,low dose lamotrigine group,medium dose lamotrigine group,and high dose lamotrigine group,with 20 rats in each group. All the rats except those in normal group were intraperitoneal injected PTZ（ 35 mg·kg^-1） per day for establishing the epileptic model; the rats in normal group were intraperitoneal injected the same volume physiological saline. After the model was successfully established,the rats in normal group were intraperitoneal injected physiological saline everyday. The rats in the other four groups were intraperitoneal injected PTZ everyday; based on this,the rats in low dose lamotrigine group,medium dose lamotrigine group,and high dose lamotrigine group were given intragastric administration of lamotrigine 20,30,60 mg·kg^-1·d^-1spectively; the rats in model group were given physiological saline for two weeks. Then the Morris water maze was used to evaluate the cognitive function of rats. The expression of Bax and Bcl-2 protein was detected by immunohistochemistry method. Results The escape incubation period of rats at each time point in the model group was significantly longer than that in normal group（ P〈0. 05）. The escape incubation period of rats at each time point in low dose lamotrigine group,medium dose lamotrigine group,and high dose lamotrigine group was significantly shorter than that in the model group（ P〈0. 05,P〈0. 01）. There was statistic difference of the escape incubation period of rats among the low dose lamotrigine group,medium dose lamotrigine group,high dose lamotrigine group（ P〈0. 05）. Space exploration experiment showed that the time staying in the platform quadrant of rats in the model group was shorter than that in normal group（ P〈0. 05）; the time staying in the platf

关 键 词：拉莫三嗪 癫痫 MORRIS水迷宫 戊四氮 Bcl-2 Bax 

分 类 号：R962[医药卫生—药理学]