不同剂量盐酸多奈哌齐对慢性癫痫大鼠空间学习记忆功能的影响

Effects of donepezil on spatial learning and memory capacity of chronic epilepsy rats kindled by pentylenetetrazole

目的探讨盐酸多奈哌齐(donepezil,Done)对戊四氮(pentylenetetrazole,PTZ)点燃慢性癫痫大鼠的认知功能损害的干预作用。方法90只雄性SD大鼠分为盐水对照组(n=18)和癫痫模型组(n=72),模型组以PTZ腹腔注射(35mg·kg-1·d-1)21d造成慢性癫痫大鼠模型后,随机分为: PTZ组,Done 0.3mg/kg组,Done 1mg/kg组,Done 3mg/kg组,4组均继续每日给予PTZ腹腔注射,Done各剂量组给予Done灌胃21d,停药后采用Morris水迷宫和跳台的方法观察PTZ点燃癫痫模型学习记忆功能的改变以及Done的影响作用。结果 PTZ组水迷宫中逃避潜伏期延长(P<0.01),平台象限游泳时间减少(P<0.01),穿越平台次数减少(P<0.05);跳台实验中反应时间延长(P<0.05),步下潜伏期缩短(P<0.05),错误次数增加(P<0.05);Done 0.3mg/kg组与PTZ组在各项观察中无明显差异,Done 1、3mg/kg组与PTZ组相比差异明显(P<0.05),但Done 1mg/kg和3mg/kg两组间相比无明显差异。结论 PTZ点燃的慢性癫痫大鼠有空间学习记忆能力障碍,Done可部分改善慢性癫痫大鼠在水迷宫和跳台实验中的空间学习能力,明显改善空间记忆能力,且具有一定的量效关系。

Objective To explore the effect of donepezil （Done） on spatial learning and memory capacity of chronic epilepsy model. Methods Ninety male Sprague-Dawley rats were divided randomly into 2 groups： control group （n = 18）, rats of which received intraperitoneal injections of 0.9% saline, and model group （n = 72）, rats of which were injected intraperitoneally with PTZ （35 mg·kg^-1 · d^-1 in 0.9% saline） for 21 days. After completely kindled, the rats in model group were randomly divided into 4 groups ： PTZ ,0.3 mg/kg Done, 1 mg/kg Done, 3 mg/kg Done. Done was orally administered for 21 d in the three Done groups, while PTZ was applied continuously in all four groups. After the last application of Done, cognitive function was tested by Morris water maze and step-down test. Results Morris water maze test results showed the escape latency was longer and total swimming times in platform quadrant as well as crossing times were less in PFZ group than in control group （P 〈 0. 05 ）. We obtained similar results in the step-down test. There were significant differences in the results of the water maze test and step-down test between 1 mg/kg Done group and control group （P 〈 0. 05）, between 3 mg/kg Done group and control group （ P 〈 0. 05 ）, but no differences between 0.3 mg/kg Done and control group （ P 〉 0. 05）, or between 1 mg/kg Done group and 3 mg/kg Done group （P 〉 0. 05 ）. Conclusion PTZ kindled rats are cognition-impaired. Donepezil can improve spatial learning capacity partially and elevate spatial memory capacity significantly in a dose-effect relationship, thus boost the cognitive function of chronic epilepsy rats.