摘要
目的探讨托吡酯(TPM)对戊四氮(PTZ)致大鼠认知功能及海马组织5-羟色胺(5-HT)和乙酰胆碱酯酶(AChE)的影响。方法28日龄健康Wistar大鼠60只,随机分为空白组、TPM一般剂量(0.018g/kg)对照组(TPM对照A组)、TPM大剂量(0.036g/kg)对照组(TPM对照B组)、PTZ(0.035g/kg)点燃模型组(PTZ组)、TPM一般剂量(0.018g/kg)治疗组(TPM治疗A组)和TPM大剂量(0.036g/kg)治疗组(TPM治疗B组),每组10只。PTZ和TPM连用4周。模型组完全点燃后各组进行Y-型迷宫学习记忆测试,免疫组织化学检测其海马组织5-HT阳性神经元的表达,化学比色法检测其海马内AChE活性。结果TPM对照A、B与空白组比较,TPM对照B组与A组比较,PTZ与空白组比较,大鼠学习能力及记忆能力均明显降低(Pa<0.001),5-HT免疫阳性神经元数量明显减少(Pa<0.001),AChE活性明显增加(Pa<0.001);TPM治疗A、B组与PTZ组相比,TPM治疗A组与TPM对照A组相比,TPM治疗B组与TPM对照B组相比,大鼠学习能力及记忆能力显著提高(Pa<0.001),5-HT免疫阳性神经元数量明显增加(Pa<0.001),AChE活性明显降低(Pa<0.001)。结论TPM可引起正常大鼠认知功能障碍,其机制可能与大鼠海马5-HT水平降低和AChE活性增加有关,其程度与TPM剂量有关;TPM良好的治疗效果掩盖了药物本身对认知功能的影响。
Objective To explore the effect of Topiramate （TPM） on cognitive function and the content of serotonin （5 - HT） and acetylcholine esterase （ACHE） activity in hippocampus of Pentetazole （PTZ） - induced epileptic rats. Methods Sixty healthy rats of 28 days were randomly divided into 6 groups ： blank control group, common dose TPM （ 0. 048 g/kg ） control group （ TPM A group ）, large dose TPM （0.036 g/kg）control group（TPM B group）,PTZ （0.035 g/kg）kindled group （PTZ group）,common dose TPM （0. 018 g/kg） treated group （PTZ and TPM A group） ,and large dose TPM （0.036 g/kg）treated group（ PTZ and TPM B group）. Every group had 10 rats. PTZ and TPM were consecutively used for 4 weeks. Every group was subjected to Y - maze to test the learning and memory after the kindled group reaching the criterion of kindling. The activity of AChE in hippocampus was measured by chemicolorimetric method ,while the expression of 5 - HT in hippocampus was determined by immunohistochemical method. Results Compared TPM - control A and B groups with blank group,comped TPM - control B group with TPM - control A group, and compared PTZ kindled group with blank group, the learning and memory ability were obviously worse （Pa 〈 0. 001 ）, the number of 5 - HT positive neuron cells in immunoreactivity was remarkably smaller （ Pa 〈 0. 001 ）, and the AChE activity in hippocampus was obviously higher （ P 〈 0. 001 ）. Compared TPM - treated A and B groups with PTZ kindled group,compared TPM - treated A group with TPM -control A group,and compared TPM -treated B group with TPM -control B group,the learning and memory ability were obviously better （P 〈 0. 001 ）,and the number of 5 - HT positive neuron cells in immunoreactivity was noticably larger （P 〈 0. 001 ） ,and the AChE activity in hippocampus was clearly lower （P 〈 0. 001 ）. Conclusions TPM is harmful to cognitive function, and the degree of cognitive functional impairment may be related to the does of drug. The cognitive functional impairment caused by TPM may be related with the decrease of 5 - HT and the increase of AChE activity in rats hippocampus. TPM may indirectly improve cognitive function by controlling the epilepsy seizure.
出处
《实用儿科临床杂志》
CAS
CSCD
北大核心
2008年第2期143-145,共3页
Journal of Applied Clinical Pediatrics
基金
佳木斯大学科研项目资助(S2006/32)
关键词
癫痫
点燃
戊四氮
海马
5-羟色胺
乙酰胆碱酯酶
托吡酯
epilepsy
kindle
pentylenetetrazol
hippocampus
serotonin
acetylcholine esterase
topiramate
