银杏叶提取物对点燃模型幼鼠学习记忆及海马NMDAR1表达的影响

Effect of extracts of Ginkgo biloba leaf on learning-memory ability and NMDA receptor 1 expression in the hippocampus in rats with kindling-induced epilepsy

目的探讨银杏叶提取物(EGb)对癫癎点燃模型幼鼠学习记忆等认知功能的影响及其可能机制,为临床应用EGb治疗癫癎儿童认知功能障碍提供实验依据。方法21,35日龄Sprague-Dawley幼鼠各40只,经初筛后随机分为生理盐水对照组(NS)、点燃对照组(PTZ)、EGb大(PTZ+EGb1)、中(PTZ+EGb2)、小(PTZ+EGb3)剂量治疗组,采用戊四氮(PTZ)致幼鼠点燃模型,以Y型电迷宫学习记忆行为训练及免疫组化检测方法,观察用药前后大鼠学习记忆功能和海马NMDAR1表达的变化。结果①治疗前后大鼠电迷宫试验达标所需电击次数:治疗前不同日龄的各个点燃组与各自NS组相比,达到学会标准所需的电击次数明显增多(P<0.01)。EGb治疗后不同剂量的各治疗组大鼠达到学会标准的次数均明显少于同龄PTZ组(P<0.01),而同龄EGb大、中、小剂量治疗组相互比较,达到学会标准所需的电击次数随治疗剂量的减少逐渐递增(P<0.01)。EGb各剂量治疗组与治疗前比较,达标次数明显减少(P<0.01或P<0.05),而NS组、PTZ组较治疗前没有明显差异(P>0.05)。②NMDAR1免疫组织化学染色:各日龄PTZ组NMDAR1免疫反应产物COD值较各自NS组明显增强(P<0.01);不同日龄各治疗组与各自PTZ组比较,随治疗剂量的增加,NMDAR1免疫反应产物COD值逐渐降低,差异均有显著性(P<0.01)。结论EGb可以明显改善发育期不同日龄点燃模型大鼠的学习记忆功能,而且剂量越大,改善作用越明显。这一作用与EGb下调反复癫癎发作后NMDAR1的过度表达有密切关系。

Objective To study the effect of extracts of Ginkgo biloba leaf （EGb）, a catalyzer of central nervous system, on learning-memory ability and possible mechanism in rats with kindling-induced epilepsy. Methods Forty postnatal day 21 （ P21 ） and 40 postnatal day 35 （ P35 ） Sprague-Dawley （SD） rats were randomly respectively assigned to five groups： normal sodium （NS） control, kindling epilepsy model, high, middle and low dosage of EGb-treated kindling epilepsy. The kindling epilepsy model was established by an intraperitoneal injection of pentetrazole （FTZ）. The learning- memory ability and NMDA receptor 1 （NMDAR1） expression in the hippocampus were measured by Y-maze test and immunohistochemistry assay respectively. Results The stimulation times for reaching to academic standard in the Y-maze test in the two ages PTZ kindling groups was significantly more than that in the corresponding NS control groups （P 〈 0.01 ）. After EGb treatment the achievement of the Y-maze test in the three treatment groups was significantly improved in a dose-dependent manner, the higher the dosage, the better the achievement （P 〈 0.01 ）. Immunohistochemistry assay showed that the expression of NMDAR1 in the two ages FTZ kindling groups was significantly higher than that in the corresponding NS control groups （ P 〈 0.01 ）. Compared with the corresponding untreated kindling model groups, the expression of NMDAR1 in the two ages EGb treatment groups was significantly reduced in a dose-dependent manner （ P 〈 0.01 ）. Conclusions EGb can improve learning-memory ability in epileptic rats at different developmental phases in a dose-dependent manner, possibly through a reduction of NMDAR1 expression in the hippocampus.