【作者】 邹纯朴；

【导师】 谢宁；

【作者基本信息】 黑龙江中医药大学 ， 中医基础理论， 2004， 博士

【摘要】 本课题通过建立β淀粉蛋白损伤离体培养的海马神经元模型，运用光、电镜技术及免疫组化、生物化学、高效液相及分子生物学等先进的检测手段和方法，从细胞及分子水平进一步探索了Aβ与老年性痴呆(AD)发生、发展密切相关的综合机制，从而全面深入地探讨了地黄饮子防治AD的作用机理。结果显示：一、地黄饮子能有效改善海马神经元生存状态，提高细胞生存活力。二、地黄饮子能明显降低海马神经元受β淀粉蛋白刺激时即早基因c-fos和c-jun的过度反应，提高海马神经元对外界不良刺激的应激性。三、地黄饮子能提高培养液中SOD、CAT和GSH-Px等抗氧化酶活性，提高对自由基清除能力。四、地黄饮子能有效抑制β淀粉蛋白损伤海马神经元所致的钙超载现象，保护细胞膜结构。五、地黄饮子是通过调控bcl-2／bax的比值、降低caspase-3基因mRNA的表达来抑制β淀粉蛋白损伤时海马神经元的过度凋亡。六、离体实验结果表明，地黄饮子对海马神经元的保护作用呈剂量依赖性，高剂量作用最好。并且明确了地黄饮子对脑内神经细胞损伤的保护作用可能是通过两种途径实现的：一是地黄饮子的某些有效成分透过血脑屏障直接发挥保护作用；二是地黄饮子通过激发促进机体保护神经细胞损伤的内源性物质的高表达达到治疗目的。更多还原

【Abstract】 On creating model of cultured hippocampal neurons injured by amyloid, we studied the mechanisms of close interrelation between amyloid and Alzheimer’s disease at cell and molecular level with advanced test methods. For example, the technique of optical lens and electron microscope , immunohistochemical method,biochemistry.molecular biology and HPLC, so as to deeply probe into the mechanisms that Decotion of Rehamanniae prelects and treats Alzheimer’s disease. The results show: 1, Decotion of Rehamanniae can significantly ameliorate the existent state of hippocampal neurons and increase the activity of neurons. 2, Decotion of Rehamanniae can effectively reduce the excessive response of Immediate-Early-Gene c-fos and c-jun when amyloid injurs hippocampal neurons, and increase the stress response of hippocampal neurons to exoteric harmful stimulation. 3, Decotion of Rehamanniae can increase the activity of antioxidant enzyme SOD. CAT, and GSH-PX in the cultured fluid, and improve the cleanup ability of free radicals. 4, Decotion of Rehamanniae can effectively control over the overloading of calcium thatBamyloid injured hippocampal neurons, and protect the frame of membrane. 5. Decotion of Rehamanniae can repress the excessive apoptosis of hippocampal neurons injured by Bamyloid through modulating the ratio of bcl-2/bax and reduce the expression of caspase-3 gene. 6, Extracorporal experimental research shows: Decotion of Rehamanniae can dose-dependly protect hippocampal neurons and the best effect is the high dose’s. And this research also shows that: the curative effect of Decotion of Rehamanniae on hippocampal neurons carries out by two approaches: 1 , By penetrating blood-brain barrier the effective components of Decotion of Rehamanniae protect hippocampal neurons from injury. 2 , Decotion of Rehamanniae achieve the aim of treatment by excitateding expression of internal substances which protect neurons from being attactted.更多还原