【作者】 崔瑛；

【导师】 颜正华； 侯士良；

【作者基本信息】 北京中医药大学 ， 中药学， 2002， 博士

【摘要】 根据祖国医学“肾生髓、充脑”理论和熟地黄补肾填精生髓的功能，结合其在治疗健忘、痴呆等疾病的复方中应用，得知熟地黄在临床上具有充养脑髓，治疗健忘证、改善学习记忆作用。我们将这种作用概括为“益智功能”，并运用药理实验方法，对熟地黄益智药效及其作用机理进行研究。 实验使用昆明种小鼠、SD雄性大鼠。采用：1、东莨菪碱忆获得障碍模型；2、乙醇记忆再现障碍模型；3、氯化铝拟痴呆模型；4、左旋谷氨酸单钠（monosodium glutamate,MSG）毁损下丘脑弓状核模型（肾阴虚学习记忆障碍模型）。试药为怀庆熟地黄水提液。阳性对照药：脑复康，六味地黄汤。实验观察熟地黄对学习记忆行为及相关神经内分泌因素的影响。结果如下： 1 熟地黄对东莨菪碱所致小鼠记忆获得障碍的影响 熟地黄能改善东莨菪碱所致小鼠记忆获得障碍。在跳台实验中，错误次数减少，潜伏期延长（P＜0.05）；降低小鼠脑组织中乙酰胆碱酯酶（Ache）活性（P＜0.01）。其作用与脑复康组相当（P＞0.05）。 2 熟地黄对40％乙醇所致小鼠记忆再现障碍的影响 熟地黄可明显改善40％乙醇所致小鼠记忆再现障碍。在跳台实验中，错误次数减少（P＜0.01），潜伏期延长（P＜0.01，P＜0.05）。其作用与脑复康组相当（P＞0.05）。 3 熟地黄对氯化铝拟痴呆模型小鼠的影响 熟地可明显改善氯化铝拟痴呆小鼠学习记忆障碍。在跳台实验中，错误次数减少（P＜0.01），潜伏期延长（P＜0.05）；在Morris水迷宫实验中，寻找平台潜伏期显著缩短（P＜0.05）。熟地黄显著降低氯化铝拟痴呆小鼠脑组织中铝离子(A1³⁺)含量（P＜0.01）、AchE活性（P＜0.05）、谷氨酸（Glu）含量（P＜0.01，P＜0.05），升高r-氨基丁酸（GABA）含量（P＜0.01，P＜0.05）。与脑复康组比较，其作用无显著性差异（P＞0.05）。 4 熟地黄对MSG大鼠学习记忆的影响 熟地黄能显著改善MSG大鼠学习记忆功能障碍。跳台实验中，熟地黄明显减少错误反应次数、延长触电潜伏期（p＜0.05）。Morris水迷宫实验中，熟地黄显著缩短寻台潜伏期（SPL）、提高跨台百分率（p＜0.05）。熟地黄降低MSG大鼠血浆皮质醇（CORT）水平（p＜0.05），和海马糖皮质激素受体mRNA（GRmRNA）表达；提高脑组织中Clu含量（p＜0.01），增加海马NMDARl受体、GABA受体、神经生长因子（NGF）、c-fos基因表达（p＜0.05，p＜0.01）。尼氏体（nissl body）染色显示：海马神经元尼氏体颗粒丰富，形态正常。 总之，1、熟地黄有改善学习记忆作用。熟地黄改善化学物质拟痴呆动物学习记忆障碍，与降低脑组织Ache活性和Clu含量、升高GABA含量有关。2、熟地黄补肾生髓充脑益智的现代机制为；降低血中CORT水平，防止继发性脑损伤；直接保护脑组织，改善脑功能，从而使反映脑功能的递质、受体、生长因子、基因表达产生有益的变化。3、将谷氨酸单钠毁损下丘脑弓状核模型作为肾阴虚学习记忆障碍模型具有可行性和实验依据，对于研究滋阴方药的益智作用、探讨机理有实用价值。更多还原

【Abstract】 This subject is based on the theory of Tradition Chinese Medicine -Kidney tonify the marrou and hasten the brain. According to the function of prepared Rehmannia Root(Chinese name: Shu Di Huang) and the use in the Complex prescriptions of treating the dementia, We realized that Shu Di Huang has the function of tonifying the brain and the marrow, improving the partial or total loss of memory in clinic. We generalize these functions as "Improving Intelligence Function". So we use the methods of pharmacology to prove that Shu Di Huang has the function of improving intelligence and to show the mechanism.We used mice and Rats to do the experiments. The models were: 1. The memory process of acquisition impaired animal model made by Scopolamine. 2. The memory process of retrieval impaired animal model made by alcohol. 3. The dementia animal model made by A1C13. 4. The dementia of the Kidney-Yin animal model made by Monosodium Glutamate(MSG). The detected medicine was Shu Di Huang, the positive contrast medicine were Piracetam tablet and Liu Wei Di huang Decoction. We observed the influence of Shu Di Huang on the behavior of leanring and memory and we detected the the related neuroendocrine factors.The results were:1 .Effects of Shu Di Huang on the memory process of acquisition impaired of mice by Scopolamine.Shu Di Huang could improve the memory process of acquisition impaired cause by Scopolanine on mice. In Ssep down test, Shu Di Huang made the mice reduce the mistakes and prolong the incubation period(p<0.05),decreased the activity of acetylcholinesterase (AchE) (p<0.01), it can be compared with Piracetam group(p>0.05).2.Effects of Shu Di Huang on the memory process of retrieval impaired of mice by alcohol.Shu Di Huang could improve the memory process of retrieval impaired caused by forty percent alcohol on mice significantly. In step down tests, Shu Di Huagn made the mice reduce the times of mistakes(p<0.01) and prolong the incubation period (p<0.01,p<0.05),it can be compared with Piracetam group(p>0.05).3.Effects of Shu Di Huang on the dementia model animal caused by A1C13Shu Di Huang could significantly improve the learning ability of the dementia model mice. In step down tests the times of mistakes lowed(pO.Ol), the incubation period prolonged(p<0.05). In Morris water maze tests, Shu Di Huang made the model mice shorten the incubation period of seeking the platform(p<0.05). At the same time, Shu Di Huang decreased the content of Al3+in the brain of the dementia model mice(pO.Ol), and decreased the activityof AchE(p<0.05), decreased the level of Glutamic acid(Glu) and increased the level of Y -Aminobatyric acid(GABA) in mice brain greatly(p<0.01,p<0.05). There is no significant difference among Shu Di Huagn groups and Piracentan group(P.O>05).4.Effects of Shu Di Huang on the deficiency of the kidney-yin rants caused by MSG.Shu Di Huang could improved the function of learning and memory disturbance of rats caused by MSG greatly. In step down tests, Shu Di Huang could decrease the times of mistakes and prolong the incubation period(p<0.05). In Morris water maze tests, Shu Di Huang made the model animals shorten the incubation period of seeking the platform, and improved the rate percent through the platform position(p<0.05).At the same time, Shu Di Huang decreased both the level of cortisol(CORT) in the plasma(p<0.05) and expression of mRNA of glucocorticoid receptor(GRmRNA) in hippocampus; increased both the content of Glu in brain and the expression of hippocampal NMDAR1 ,GABAR, nerve growth factor(NGF), c-fos gene (p<0.05,P,0.01). Nissl body staining showed that hippocampal neurn nissl body granule is richful and the appearance is normal.In a word, (1) Shu Di Huang has the function of improving intelligence. The mechanism that Shu Di Huang improve the process of memory impaired caused by Chemical substance has relation with the decrease of the activity of AchE and the content Glu in brain, and is related to the increase of the content of GABA. (2) The effects of Shu Di Huang o更多还原