淫羊藿苷和固本方改善肾虚型老年痴呆模型鼠海马神经元突触损伤

Icariin and Guben Formula ameliorates kidney deficiency of senile dementia-induced synapse lesions

目的:观察淫羊藿苷和固本方对肾虚型老年痴呆模型鼠海马神经元突触形态的影响。方法:选用健康成年SD大鼠52只,随机分为对照组、肾虚型老年痴呆模型组、淫羊藿苷治疗组和固本方治疗组,每组13只。采用皮下注射氢化可的松(15mg·kg^-1·d^-1),连续14d,第15天侧脑室定位注射Aβ_(25-35)建立肾虚型老年痴呆大鼠模型。淫羊藿苷及固本方治疗4周后,通过Morris水迷宫测试大鼠空间学习记忆能力。采用高尔基染色技术统计分析海马DG区神经元树突一级分支上树突棘的密度;通过超微电镜分析突触超微结构;提取海马组织采用突触后致密物95(PSD95)及NMDA受体亚基1(GluN1)抗体检测突触后相关蛋白的表达。结果:与肾虚型老年痴呆模型组比较,淫羊藿苷治疗组和固本方治疗组在原目标象限区域停留时间的比例和穿越原平台的次数显著增加(P<0.05);与对照组比较,肾虚型老年痴呆模型组海马神经元树突棘数目显著减少(P<0.05),突触后致密物显著变薄(P<0.05),PSD95及GluN1蛋白的表达显著减少(P<0.05);与肾虚型老年痴呆模型组比较,淫羊藿苷治疗组和固本方治疗组海马神经元树突棘数目显著增多(P<0.05),突触后致密物显著增厚(P<0.01,P<0.05),PSD95及GluN1蛋白的表达显著增加(P<0.05,P<0.01)。结论:淫羊藿苷和固本方有效改善海马神经元突触损伤,改善空间学习记忆能力。

Objective:To observe the effects of icariin(ICA)on kidney deficiency type of senile dementia model rats on synapse lesions in hippocampus.Methods:SD rats randomly divided into control group,kidney deficiency type of senile dementia model group,ICA cure group,Guben Formula cure group,13 rats in each group.The animals were administered ydrocortisone(15 mg·kg^-1·d^-1)by subcutaneous injection for 14 d,lateral ventricle injection of Aβ25-35 on 15 th day establish the model of kidney deficiency type of senile dementia.Then,spatial learning and memory ability was detected by Morris water-maze.Further,dendritic spines density of neurons in hippocampus was was analyzed by Golgi staining technique.To understand the ultrastructural of synapse,we observed the morphologies in hippocampal neurons using Tecnai G220 TEM.Results:Compared with the kidney deficiency type of senile dementia model group,ICA and Guben Formula improved spatial memory retention damage with more percentage of residence time in target quadrant and number of target flatform crossing(P<0.05).Compared with control group,the density of the dendritic spines,thickness of postsynaptic density,PSD95 and GluN1 proteins was decreased in kidney deficiency type of senile dementia model group(P<0.05).ICA and Guben Formula enhanced the density of the dendritic spines and thickness of postsynaptic density,with upregulation PSD95 and GluN1 proteins(P<0.05,P<0.01).Conclusion:ICA and Guben Formula can effectively improve the synaptic damage of hippocampal neurons and the ability of spatial learning and memory.