银杏内酯联合胰岛素对拟阿尔茨海默氏病大鼠学习记忆的作用

Effect of gingkgolide combined with insulin treatment on learning ability of AD-like model rats

目的:观察银杏内酯和胰岛素联合应用对拟阿尔茨海默氏病(Alzheimerdisease,AD)大鼠学习记忆能力的影响,并探讨其作用的可能机制。方法:大鼠海马CA1区微量注射冈田酸(Okadaicacid,OA),建立AD大鼠模型,侧脑室微量注射胰岛素、胃灌注银杏内酯进行预处理。检测大鼠学习记忆能力,观察海马CA1区神经原纤维缠结(neurofibrillarytangle,NFT)及神经胶质原纤维酸性蛋白(glialfibrillaryacid-icprotein,GFAP)的表达。结果:与模型组比较,银杏内酯组、联合组的学习记忆能力明显改善(P<0.05);CA1区NFT和GFAP表达减少(P<0.05),联合组更为显著(P<0.05)。结论:银杏内酯和胰岛素联合应用对拟AD大鼠学习记忆的改善作用强于单用银杏内酯,同时减少海马CA1区神经细胞Tau蛋白的磷酸化以及神经胶质细胞增生和肥大,这可能是改善模型鼠学习记忆能力的机制之一。

AIM： To examine the effects of the gingkgolide combined with insulin treatment on the learning ability of the AD-like model rats and explore the possible mechanism of its effect. METHODS： The AD-like animal models were established by injection of okadaic acid （OA） in the hippocampal CA1 area, and pretreatment was administered by injecting insulin in the lateral brain ventricle and forced feeding with gingkgolides. The learning capability of the rats was examined by means of Morris water maze, and the expressions of neurofibrillary tangle （NFT） and glial fibrillary acidic protein （GFAP） in the CA1 area were observed through Bielschowsky-dyeing and immunohistochemistry, respectively. RESULTS： The impaired learning ability of the rats in the gingkgolide combined with insulin group was greatly improved compared with that in the group treated with gingkgolide alone （P 〈 0.05）. Meanwhile, the expressions of GFAP and NFT in the CA1 area in the gingkgo group and gingkgo combined with insulin group were significantly reduced, and even lower in the combined group than in the gingkgo group （P 〈 0.05）. CONCLUSION： The gingkgolide combined with insulin treatment exerts a stronger improving effect on the learning ability of the AD-like model rats, possibly by reducing phosphorylation of Tau in neurons and inhibiting hyperplasia of the glial cells in the hippocampal CA1 area.