银杏内酯和胰岛素对拟AD模型大鼠学习记忆的影响

A Study of the Effect of Ginkgolides and Insulin on Alzheimer's Disease-like Model Rats

目的:建立拟AD大鼠模型,研究银杏内酯和胰岛素对拟AD模型大鼠学习记忆的影响。方法:采用冈田酸(OA)海马CA1区微量注射建立拟AD大鼠模型,分为银杏内酯组,胰岛素组。银杏内酯组腹腔注射银杏内酯,胰岛素组侧脑室微量注射速效基因合成人胰岛素,分别设对照组。冈田酸末次注射2周后水迷宫行为学试验检测其学习记忆,B ielschowsky染色观察海马CA1区老年斑(SP)和神经原纤维缠结(NFT)。结果:拟AD模型组定向航行试验于第2天开始平均逃避潜伏期与对照组比较明显延长(P<0.05或P<0.01),空间探索试验原站台象限活动时间明显缩短(P<0.01);与拟AD模型组比较,银杏内酯组及胰岛素组平均逃避潜伏期明显缩短(P<0.05或P<0.01),原站台象限活动时间明显延长(P<0.01)。B ielschowsky染色观察对照组大鼠海马CA1区未见明显改变,拟AD模型组大鼠海马CA1区形成NFT,细胞外有SP;银杏内酯组和胰岛素组大鼠海马CA1区少见或未见SP或NFT。结论:银杏内酯腹腔注射或胰岛素微量侧脑室注射均可减少拟AD模型大鼠海马CA1区SP和NFT的形成,减轻OA对大鼠海马的病理损害,显著改善拟AD模型大鼠学习记忆功能。

Objective： To establish an animal model of Alzheimer＇s disease （AD） and to investigate the effect of ginkgolides and insulin on the AD-like model rats. Methods： AD-like model was established by injecting okadaic acid （OA） into hippocampal CA1 region of rats. Then, model rats were injected with ginkgolides into the abdominal cavity or were injected with insulin into the lateral ventricle of the brain. The learning and memory capabilities of treated model rats were assessed through Morris Water Maze behavioral test. Senile plaques （SP） and neurofibrillary tangles （NFT） of hippocampus were observed by Bielschowsky stain. Results： In three weeks, compared with model rats that without the treatment of ginkgolides or insulin, the treated rats had shorter average escape latency in place navigation test （P 〈 0.05 or P 〈 0.01） and longer swimming time in the third quadrant in spatial probe test, after the platform was removed （P 〈 0.01）. It was observed that SP and NFT in hippocampal CA1 region were reduced or disappeared in those treated rats. Conclusions： Ginkgolides and insulin can inhibit the formation of SP and NFT and alleviate the damage of hippocampus neurons induced by OA and improve the learning and memory capabilities of the model rats.