SB-271046对匹罗卡品致痫大鼠空间学习记忆的影响  

Effects of SB-271046 on spatial learning-memory in pilocarpine-induced epileptic rats

作　　者：黄明珠[1] 黄华品[1] 林婉挥[1] 陈圣根[1] 

机构地区：[1]福建医科大学附属协和医院神经内科,福建福州350000

出　　处：《中风与神经疾病杂志》2018年第1期4-9,共6页Journal of Apoplexy and Nervous Diseases

基　　金：国家自然科学基金(面上项目)资助(No.81371426)

摘　　要：目的观察5-羟色胺6受体拮抗剂SB-271046对匹罗卡品致痫大鼠空间学习记忆的作用效应。方法成年雄性SD大鼠分为两组:空白对照组(Vehicle组,n=10),氯化锂-匹罗卡品组(Lithium chloride-Pilocarpine,LiCl-PILO组,n=40)。首先根据注射LiCl-PILO后是否出现癫痫持续状态(Status Epilepticus,SE),出现SE者纳入实验,未出现SE和死亡者则剔除;然后再随机分为3组:模型组即侧脑室注射羟丙基-β-环糊精(Hydroxypropyl-β-cyclodextrine,HP-β-CD),4μl;药物组按不同剂量分为2组,即侧脑室注射N-[4-Methoxy-3-(4-methyl-1-piperazinyl)-phenyl]-5-chloro-3-methylbenzo-thiophene-2-yl-sulphonamide monohydrochloride(SB-271047)剂量为10μg,4μl和侧脑室注射SB-271046剂量为20μg,4μl。结果在Y迷宫自主交替行为实验中,模型组自主交替率显著下降(P<0.01),药物组显著提高尤其是20μg剂量组(P<0.05)。在Y迷宫新奇事物探索实验中,模型组的新臂时间比显著下降(P<0.01),药物组有提高趋势(P>0.05)。在Morris水迷宫定位航行实验中,模型组平均潜伏期延长显著延长(P<0.01),药物组明显缩短尤其是20μg剂量组(P<0.05)。在Morris水迷宫空间探索实验中,模型组平均潜伏期延长,穿越平台次数减少,原平台象限停留时间缩短(P<0.05),药物组有改善趋势(P>0.05)。结论 SB-271046可以改善癫痫大鼠的空间学习记忆,主要作用于记忆获得巩固阶段,20μg剂量作用明显。Objective Our primary objective is to investigate the effects of 5-HT6 receptor antagonist SB-271046 on spatial learning-memory in pilocarpine-induced epileptic rats. Methods 50 male adult Sprague-Dawley rats were divided into 2 groups,vehicle control group（ n = 10） and pilocarpine（ PILO） treated group（ n = 50）. Status epilepticus（ SE） of rats was induced by intraperitoneal（ i. p.） injection of LiCl-pilocarpine. According to Racine classify,seizures up to IV and last more than 30 mins are supposed to be SE. Rats with successful SE were then divided into 3 groups： mode control group（ HP-CD,lateral ventricle（ LV） injection with HP-β-CD,4 μl）,10 μg-SB271046 group（ 10 μg-SB,LV injection with SB-271046,4 μl）,20 μg-SB271046 group（ 20 μg-SB,LV injection with SB-271046,4 μl）. Unsuccessful SE rats and died rats were both excluded from our experiment. Spatial learning-memory was evaluated to all groups by Y-maze and Morris water maze after 6 weeks. Results In Y-maze spontaneous alternation behavior test（ SAB）,We found significant decreasing of alternation rate in HP-CD group（ P〈0. 01）. Besides,we saw reversion of alternation rate in the rats in SB-271046 injected groups,especially 20 μg-SB271046 group（ P〈0. 05）. In Y-maze novel object discrimination 4 h ITI test（ NOD）,new arm percentage of HP-CD also decreased significantly（ P〈0. 01）,but SB-271046 didn＇t reverse this defect. In Morris water maze acquisition stage,the latency of different groups were gradually shorten from day 1 to day 5; meanwhile,the mean latency of the rats in HP-CD was prolonged significantly（ P〈0. 01）,the most obvious improvement also was found in 20 μgSB271046 group（ P〈0. 05）. In retention stage,the results of 3 items： means latency,numbers of crossing target and percentage of performance time in target zone indicated the memory of rats in HP-CD group were damaged,SB-271046 didn＇t reverse the defects. Conclusion 5-HT6 receptor antagonist SB-271046 can reverse e

关 键 词：癫痫 5-HT6受体 SB-271046 MORRIS水迷宫 Y迷宫 

分 类 号：R742.1[医药卫生—神经病学与精神病学]