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

doi:10.3969/j.issn.2095-4344.2016.49.002

Abstract

Abstract:

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 in the high-dose drug group was significantly higher than that in the model and low-dose drug groups, high-dose drug relieved the suppression of long term potentiation, and the synaptic plasticity was significantly improved. (3) Bushen Yizhi Decoction could significantly decrease the levels of tumor necrosis factor-α, interleukin-1 and malondiadehyde as well as the activity of acetylcholin esterase, and significantly increase the activity of superoxide dismutase and choline acetyltransferase (P < 0.05). (4) These results suggest that the nootropic effect of Bushen Yizhi Decoction on the rat model of Alzheimer’s disease may be related with the inhibition of inflammation, adjustment of cholinergic nerve transmitter activity and antioxidation.

中国组织工程研究杂志出版内容重点：肾移植；肝移植；移植；心脏移植；组织移植；皮肤移植；皮瓣移植；血管移植；器官移植；组织工程

Key words: Models, Animal, Drugs, Chinese Herbal, Alzheimer Disease, Antioxidants, Tissue Engineering

CLC Number:

R318

Wang Gai-feng. 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[J]. Chinese Journal of Tissue Engineering Research, 2016, 20(49): 7307-7313.

Figures/Tables 1

2.1 实验动物数量分析 50只大鼠造模成功后，所有大鼠无死亡情况，均顺利进入后续试验。 2.2 模型稳定性 D-半乳糖致老年痴呆是一种已经很成熟的老年痴呆模型，有大量研究证实这种模型方法能很好地模拟人类痴呆情况。 2.3 Morris水迷宫测试结果 Morris水迷宫实验结果显示，定位航行实验中，与对照组相比，模型组在的逃避潜伏期明显延长；与模型组相比，药物组逃避潜伏期均明显缩短(表1)，表明大鼠的空间学习能力较模型组有所提高。空间探索实验中，模型组大鼠在目标象限内游泳的距离比对照组明显降低；与模型组相比，药物组大鼠在目标象限内游泳的距离均增多(表2)。 2.4 电生理学检测结果对各组大鼠进行高频刺激后，群体峰电位的幅度都较刺激前有所增加，表明各组大鼠海马都有长时程增强的形成(表3)，高频刺激后，模型组群体峰电位幅度有一定程度的增强，但明显低于对照组；补肾益智方20 g/kg组和补肾益智方5 g/kg组经过高频刺激后群体峰电位幅度明显大于模型组；从刺激后群体峰电位幅度变化可看出，模型组和在60 min内群体峰电位幅度均低于对照组、补肾益智方20 g/kg组和补肾益智方5 g/kg组，对照组、补肾益智方20 g/kg组和补肾益智方5 g/kg组在所记录的60 min内群体峰电位幅度变化不是很明显。 2.5 对老年痴呆模型的抗氧化作用与胆碱能神经影响补肾益智方对老年痴呆模型大鼠大脑组织超氧化物歧化酶活性、丙二醛及单胺氧化酶B水平的影响，实验结果见表4，结果表明，与对照组相比，老年痴呆模型组大鼠大脑中超氧化物歧化酶活性显著降低，丙二醛水平显著提高，给药补肾益智方后，补肾益智方20 g/kg， 5 g/kg组与模型组相比，大鼠大脑组织中超氧化物歧化酶活性显著提高，丙二醛与单胺氧化酶B水平显著降低。补肾益智方对老年痴呆模型大鼠脑组织胆碱乙酰基转移酶与乙酰胆碱酯酶活性的影响，实验结果见表5，结果显示，补肾益智方20 g/kg，5 g/kg组与模型组相比，大鼠大脑组织中乙酰胆碱酯酶活性显著提高，胆碱乙酰基转移酶活性显著降低。 2.6 补肾益智方对脑内炎症反应的影响补肾益智方对老年痴呆模型海马组织肿瘤坏死因子α及白细胞介素1的影响，实验结果见表6，结果表明，与对照组相比，老年痴呆模型组大鼠海马组织炎症因子肿瘤坏死因子α及白细胞介素1水平显著提高，补肾益智方20，5 g/kg组与模型组相比，大鼠脑组织炎症因子肿瘤坏死因子α及白细胞介素1水平显著降低。"

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