【作者】 申丽红；

【导师】 张均田；

【作者基本信息】 中国协和医科大学 ， 神经药理学， 2003， 博士

【摘要】 中枢神经系统的大部分神经元处于终末分化状态，受损后无法再生。近年来，研究者在胚胎神经组织和成年脑内均找到了这样一群特殊的神经细胞，它们不但终生保有自我更新能力，而且还具备了多向分化的潜能，因而被称为“干细胞”或“前体细胞”。从理论上讲，这类细胞有可能能够替代那些由于疾病，外伤等原因而受到损害的神经元，因而有极大的应用前景。目前阶段，与此相关的研究主要集中在两个方面：1)从胚胎或成年脑组织中分离得到神经干细胞(NSCs)／神经前体细胞(NPCs)，在体外对其进行培养，扩增和某些基因操作，然后再将它们移植回受损的脑组织中；2)运用某些手段诱导体内的NSCs／NPCs发生增殖，分化，进而达到所谓“自我修复”的目的。十年来，以上两方面的研究工作吸引到了大批科学家的参与，并且都取得了一些突破性的进展。值得注意的是，这些工作大多以啮齿类动物为研究对象。一旦涉及到人类，神经干细胞的体外培养，移植等项工作便会遇到来源不足，不符合社会伦理道德观念等多方面的问题。因此，越来越多的研究者把目光转向了对体内干细胞进行诱导性操作这一方向。从药理学角度考虑，积极寻找能够影响NPCs增殖分化功能的化合物，无疑会为神经系统疾病的治疗打开一条全新的思路。 作为一种珍贵的滋补品，人参在中医中的应用已有了两千多年的历史。现代医学证明，人参具有促智，抗衰老等多种药理作用。人参皂甙Rgl是从人参中分离提取出的活性单体成分之一，它具备了人参促进学习记忆，延缓与衰老相关的功能低下等多项功效。本组以前的研究工作发现，Rgl能够通过促进脑内蛋白质合成，增加断乳小鼠脑皮层厚度和突触数目来提高啮齿类动物神经功能的可塑性。由于成年哺乳动物脑内NPCs的存在也被认为是一种神经可塑性的体现，可以设想，对脑内NPCs增殖分化状态产生影响很可能是Rgl发挥中枢药理作用的机制或途径之一。基于此，我们设计进行了本项实验，从体内外两个角度观察了Rgl对NPCs增殖，分化和存活等多项功能的影响。更多还原

【Abstract】 Most neurons in CNS are terminally differentiated and are, thus, not replaced after neuronal cell death. However, self-renewing cells with multilineage potential, designated stem cells or progenitor cells, have been identified in both developing and adult brain in mammals. This finding raises the possibility that human neurons depleted by disease or injury could be replenished. At present, there are two active directions which have been studied in terms of using neural stem cells (NSCs) or neural progenitor cells (NPCs): 1) Isolate NSCs/NPCs from fetal or adult brain, expand, engineer them in vitro and then transplant them back to the injured brain. 2) Induce endogenous NSCs/NPCs to proliferate and differentiate in vivo to achieve self-repair. In the past decade, both subfields have attracted a large number of investigators and both have got promising results, especially in rodent. But when it comes to human being, the first group met with several difficulties ranging from ethical concerns to limited supply. So, it will be of great value to find out drugs that can affect the proliferation and /or differentiation ability of NPCs both in vitro and in vivo.Ginseng has been used as a tonic in Chinese traditional medicine for over two thousand years. It has been proved to have various pharmacological actions on the CNS including nootropic and anti-aging effects. Ginsenoside Rg 1 is one of the most active ingredients in ginseng and shares many of its effects, such as facilitating learning, memory and alleviating age related decline of functions. In our previous studies, Rgl was found to accelerate protein biosynthesis, enhance the thickness of cortex and the density of synapses in rodent brain. As all above effects of Rgl had something to do with brain plasticity and the existence of NPCs in brain is also a new mechanism underlying functional plasticity of brain, it is possible that更多还原