补肾益智方对D-半乳糖联合β-淀粉样蛋白25-35致老年痴呆模型大鼠的作用及机制  

Effects of Bushen Yizhi Decoction on Alzheimer's disease model rats induced by D-galactose combined with amyloid-beta 25-35 and the underlying mechanism

作　　者：王改凤[1] 

机构地区：[1]河南中医药大学第二附属医院脑病一区,河南省郑州市450002

出　　处：《中国组织工程研究》2016年第49期7307-7313,共7页Chinese Journal of Tissue Engineering Research

基　　金：郑州市科技发展计划项目(2010SFXM273)~~

摘　　要：背景:中药复方具有多靶点的作用特点,能通过多个环节对中枢胆碱能神经系统进行调节,有效改善患者的认知功能。研究证明,补肾益智方可以改善老年痴呆患者的症状,提高生活质量。目的:探讨补肾益智方对D-半乳糖联合β-淀粉样蛋白25-35致老年痴呆模型大鼠的作用及其机制。方法:选用健康成年SD大鼠,随机分为对照组、模型组、阳性药物组(多奈哌齐组0.3 g/kg)、补肾益智方20 g/kg组及补肾益智方5 g/kg组,每组10只,采用皮下注射D-半乳糖联合双侧海马注射β-淀粉样蛋白25-35构建痴呆大鼠模型。用补肾益智方药液灌胃治疗8周后,釆用Morris水迷宫测试检测大鼠的学习记忆能力;采用高频刺激Schaffer侧支,在同侧海马CA1区诱导长时程增强的方法检测大鼠海马神经元突触可塑性的变化;同时检测大鼠脑组织多种指标,包括超氧化物歧化酶活性、丙二醛、单胺氧化酶B、胆碱乙酰基转移酶、乙酰胆碱酯酶、肿瘤坏死因子α、白细胞介素1等。结果与结论:(1)水迷宫实验中补肾益智方组可显著改善大鼠的学习记忆能力,模型组与对照组相比海马CA1区长时程增强幅度显著降低(P<0.05);(2)补肾益智方5 g/kg组与模型组比较,群体峰电位幅度差异无显著性意义;补肾益智方20 g/kg组群体峰电位幅度明显高于模型组和补肾益智方5 g/kg组,能减轻D-半乳糖联合β-淀粉样蛋白25-35对海马CA1区长时程增强的抑制作用,改善突触功能的可塑性;(3)补肾益智方组能显著降低肿瘤坏死因子α和白细胞介素1的水平(P<0.05),明显提高胆碱乙酰基转移酶和超氧化物歧化酶活性(P<0.05),降低乙酰胆碱酯酶活性及丙二醛水平(P<0.05);(4)结果提示,补肾益智方对阿尔茨海默病大鼠模型学习记忆的改善作用可能与抑制脑内炎症反应、调节胆碱能系统、抗氧化作用等有关。BACKGROUND： Traditional Chinese medicine compound has the characteristics of multiple targets, which can regulate the central nervous system through a plurality of links, and can effectively improve the cognitive function of patients. Bushen Yizhi Decoction has been proven to improve the symptoms of patients with Alzheimer＇s disease, thereby improving the quality of life. OBJECTIVE： To explore the effects of Bushen Yizhi Decoction on learning and memory abilities in seniledementia rats induced by D-galactose combined with amyloid-beta 25-35 and the underlying mechanism. METHODS： Healthy adult Sprague-Dawley rats were equivalently randomized into groups of control, model, positive drug（0.3 g/kg donepezil）, high-dose drug（20 g/kg Bushen Yizhi Decoction） and low-dose drug（5 g/kg Bushen Yizhi Decoction）. Model rats with Alzheimer＇s disease were established by subcutaneous injection of D-galactose and bilateral hippocampuses injected with amyloid-beta 25-35. After 8-week treatment with intragastric administration of Bushen Yizhi Decoction, the spatial learning and memory capacity were examined by the Morris water maze. High frequency stimulation was given on CA3 Schaffer collateral-commissural pathway, and long-term potentiation in hippocampal CA1 region was recorded to detect the change of synaptic plasticity in rat＇s hippocampal neurons, and the levels of superoxide dismutase, malondiadehyde, monoamine oxidase B, choline acetyltransferase, acetylcholin esterase, tumor necrosis factor-α and interleukin-1 were detected. RESULTS AND CONCLUSION：（1） Morris water maze tests showed that the groups of Bushen Yizhi Decoction could remarkably improve the spatial learning and memory capacity of rats. Compared with the control group, the long-term potentiation in hippocampal CA1 region was significantly suppressed in model rats（P 〈0.05）.（2） There was no significant difference in the phase-shift amplitude between the model and the low-dose drug groups; however, the phase-shift amplitude i

关 键 词：动物 模型 中草药 阿尔茨海默病 抗氧化剂 组织工程 实验动物 神经损伤与修复动物模型 补肾益智方 老年痴呆 抗氧化 炎症因子 

分 类 号：R318[医药卫生—生物医学工程]